This study proposes the reverse cumulative distribution curve (RCDC) for optimal dose selection and a scaled logit model for estimating protection in EV71 vaccine development.

Data were from a phase 2 trial involving infants and young children randomized to receive either 640 U with or without adjuvant, 320 U with adjuvant, 160 U with adjuvant EV71 vaccines, or placebo. RCDCs were constructed using neutralizing antibody titers 28 days post-vaccination. Robustness of RCDC parameters was assessed via coefficient of variation for the area under the curve (AUC), the relative optimal point, median on the curve, and antibody titer of the point of maximum curvature, with geometric mean titer (GMT) as control. The scaled logit model estimated protection against EV71-associated disease for the selected optimal dose.

The AUC and relative optimal point demonstrated greater robustness than GMT. The 640 U with adjuvant dose had the highest AUC (0.64, 95% CI: 0.61-0.66), sum of coordinates of the relative optimal point (1.40, 95% CI: 1.34-1.43), and the highest estimated protection (93.36%, 95% CI: 79.91-97.86).

AUC and relative optimal point of RCDC are effective for early vaccine dose screening, with protection estimated by the scaled logit model.

Porcine epidemic diarrhea virus (PEDV) causes significant global agricultural losses. Despite commercial inactivated and live attenuated vaccines, persistent outbreaks underscore the need for more effective solutions. Here, we isolated a novel Chinese PEDV variant, PEDV ShXXY2-2023, with amino acid substitutions in key neutralizing epitopes (N-terminal domain, receptor-binding domain, and CO-26K equivalent epitope) compared to vaccine strains. An inactivated ShXXY2-2023 vaccine induced higher neutralizing antibodies and superior cross-protection versus commercial vaccines. Vaccinated sows conferred enhanced protection to offspring, improving piglet survival post-challenge. Maternal serum neutralizing antibody titers correlated strongly with piglet survival; titers of 1:377-1:774 at one week prepartum yielded >80% protective efficacy. These findings emphasize neutralizing antibodies' critical role in PEDV prevention and position ShXXY2-2023 as a promising vaccine candidate, with broader implications for coronavirus vaccine development.

Evidence regarding the comparative safety of different COVID-19 vaccines remains limited. This study aims to characterize and compare the safety profiles of five COVID-19 vaccines in terms of adverse reactions after immunization.

We conducted a retrospective analysis of adverse reactions reported among adults aged 18-59 years from nine clinical trials. The analyzed vaccines included inactivated, recombinant protein, intranasal influenza-vectored, aerosolized and intramuscular Ad5 vectored COVID-19 vaccines. Factor analysis and association rule analysis were used to characterize adverse reaction patterns, while multivariate logistic regression was employed to assess the influence of vaccine type and demographic factors.

Inactivated, recombinant, and intramuscular Ad5 vectored vaccines commonly caused injection site pain, fatigue, headache, and pyrexia from the SOC of 'General disorders and administration site conditions.' Intranasal influenza-vectored vaccines mainly cause respiratory symptoms such as rhinorrhea and nasal congestion, while dry mouth and oropharyngeal pain from 'Gastrointestinal disorders' were primarily observed in aerosolized Ad5 vectored vaccines. Younger age (p < 0.001), female sex (p = 0.001), comorbidities (p < 0.001), and intramuscular Ad5 vectored vaccines (p < 0.001) were significantly associated with higher adverse reaction risks.

COVID-19 vaccines developed through different technological approaches have distinct adverse reaction profiles.

The emergence of the SARS-CoV-2 virus worldwide led to the call for the development of effective and safe vaccines to contain the spread and effects of COVID-19. Using information from 40 publications, including clinical trials and observational studies from 2019 to 2024, this review assesses the effectiveness, safety, and limitations of four major vaccines: Sinopharm (BBIBP-CorV), Moderna (mRNA-1273), Pfizer-BioNTech (BNT162b2), and CoronaVac. Pfizer-BioNTech and Moderna's mRNA vaccines proved to be more effective than others; Moderna's vaccines showed an efficacy of 94.1 % against symptomatic infection, while Pfizer-BioNTech's vaccines showed an efficacy of up to 95 %, against severe diseases and hospitalization. These vaccinations, which included protection against Omicron and Delta variants, offered notable protection against serious illness, hospitalization, and mortality. Severe adverse events were rare while most adverse events were mild to moderate, such as headaches, fatigue, and localized reactions. In contrast, inactivated virus vaccines such as Sinopharm and CoronaVac with efficacies ranging from 50 to 79 % against symptomatic infection showed lower levels of effectiveness. In Phase 3 trial, Sinopharm showed 72.8 % efficacy, whereas CoronaVac demonstrated roughly 67 % efficacy in population against hospitalization and severe disease. Booster doses were required for adequate immunological response, especially against novel strains, as these vaccinations proved to be less effective in older populations. They showed considerable safety profiles, with mild side effects, but their low immunogenicity is concerning. This review emphasizes the importance of continuously evaluating vaccines in response to the evolving virus, essential for improving international immunization programs.

SARS-CoV-2, the virus causing COVID-19, poses significant health threats due to its high transmissibility and potential for severe respiratory complications. T cells, central to adaptive immunity, also interact with innate immunity, playing a pivotal role in coordinating defenses and eliminating infected cells. Single-cell RNA sequencing (scRNA-seq) has provided more subtle heterogeneity, rare subpopulations, or new subpopulations that are at the district differentiation stage or with specific function. Thus, elucidating how T cell heterogeneity impacts COVID-19 disease severity remains a critical question requiring comprehensive analysis. This review revealed the heterogeneity of the host T cells, including conventional T cells (CD8+, CD4+ T cells) and unconventional T cells, including natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) and gamma-delta T (γδT) cells in COVID-19 patients with different clinical manifestations. Severe COVID-19 had marked lymphopenia, excessive activation, elevated exhaustion and reduced functional diversity of T cells. Pathogenic contributions arise from dysregulated cytotoxic T cells, Treg cells and unconventional T cells collectively driving systemic hyperinflammation and tissue injury. Current therapeutic strategies targeting T cells-such as enhancing virus-specific T cell responses, reverting T-cell exhaustion and alleviating inflammation-exhibit inconsistent efficacy, underscoring the need for combinatorial approaches. This review highlights how scRNA-seq deciphers T cell heterogeneity and dysfunction in COVID-19. By targeting T cell exhaustion, inflammation, and subset-specific deficits, these insights pave the way for therapies and vaccines.

Human coronaviruses (CoV) cause respiratory infections that range from mild to severe. CoVs are a large family of viruses with considerable genetic heterogeneity and a multitude of viral types, making preventing and treating these viruses difficult. Comprehensive treatments that inhibit CoV infections fulfill a pressing medical need and may be immensely valuable in managing emerging and endemic CoV infections. As the main protease (Mpro) is highly conserved across many CoVs, this protease has been identified as a route for broad CoV inhibition. We utilize the advanced generative chemistry platform Chemistry42 for de novo molecular design and obtained novel small-molecule, non-peptide-like inhibitors targeting the SARS-CoV-2 Mpro. ISM3312 is identified as an irreversible, covalent Mpro inhibitor from extensive virtual screening and structure-based optimization efforts. ISM3312 exhibits low off-target risk and outstanding antiviral activity against multiple human coronaviruses, including SARS-CoV-2, MERS-CoV, 229E, OC43, NL63, and HKU1 independent of P-glycoprotein (P-gp) inhibition. Furthermore, ISM3312 shows significant inhibitory effects against Nirmatrelvir-resistant Mpro mutants, suggesting ISM3312 may contribute to reduced viral escape in these settings. Incorporating ISM3312 and Nirmatrelvir into antiviral strategy could improve preparedness and reinforce defenses against future coronavirus threats.

COVID-19, caused by SARS-CoV-2 infection, left widespread impacts worldwide. In Brazil, immunization reduced incidence rates. However, six months later, waning neutralizing antibody titers and new immune-evading variants increased cases, resulting in recurring waves. This study evaluated hospitalized COVID-19 patients after the vaccination rollout, comparing the clinical outcomes between vaccinated and unvaccinated patients. Positive samples underwent nucleotide sequencing. A total of 218 patients were included; 202 (92 %) had vaccination data, 98 received at least one dose, and 64 completed the vaccination schedule, predominantly with CoronaVac®. Vaccinated individuals were older on average since the campaign was primarily conducted among the elderly. The Gamma variant predominated during the study period. While not statistically significant, trends indicated greater respiratory assistance needs, more extended hospital stays, and increased ICU time among unvaccinated patients. Mortality was 45 % in vaccinated and 37 % in unvaccinated groups, with no notable difference. However, patients with a complete vaccination schedule showed a higher chance of survival, though not significant (p = 0.11). The factors significantly associated with higher mortality were older patients, those requiring vasopressor drugs, and mechanical ventilation. These findings provide clinical, epidemiological, and phylogenetic insights into COVID-19 patients during vaccination implementation. They underscore the need to evaluate vaccine effectiveness against circulating variants and highlight the importance of complete vaccination schedules for improving patient outcomes.

This research attempted to compare the immune response of Pfizer, Sinovac, and Influvac tetra vaccines in addition to comparing their effects on the submandibular glands (SMGs) and associated lymph nodes in albino rats.

Forty rats were allocated into four groups: group Ι (control), group II (Pfizer), group III (Sinovac) and group IV (Influvac tetra). Serum immunoglobulins G and A (IgG and IgA) were measured. Then, animals were sacrificed. Histological and immunohistochemical examinations were performed on the dissected SMGs and associated lymph nodes.

The Pfizer group had the highest mean IgG and IgA readings, followed by the Sinovac, Influenza and control groups, with a significant variation between every 2 groups. Histopathological examination of the SMGs of all groups showed nearly normal gland architecture resembling the control group. However, mild changes were observed in vaccinated groups. Lymph nodes' histopathological examination revealed inactive primary lymphoid follicles in the control group. However, all vaccinated groups revealed active lymph nodes with secondary lymphoid follicles. Regarding the area percentage of CD3 immunoexpression, the greatest value was reported in Pfizer group, followed by Sinovac, Influenza and control groups, with a significant difference between Pfizer and both Sinovac and influenza groups. However, no substantial variation was observed between Sinovac and Influenza groups.

All vaccines administered were effective. The Pfizer vaccination had the most T cells and the highest serum concentrations of IgG and IgA. All vaccines generally had a satisfactory safety profile with no impact on salivary gland histology.

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna's mRNA vaccines, as well as adenovirus vector-based vaccines such as Oxford-AstraZeneca. However, the emergence of new variants and subvariants of SARS-CoV-2, characterized by enhanced transmissibility and immune evasion, poses significant challenges to the efficacy of current vaccination strategies. In this review, we aim to comprehensively outline the landscape of emerging SARS-CoV-2 variants of concern (VOCs) and sub-lineages that have recently surfaced in the post-pandemic years. We assess the effectiveness of existing vaccines, including their booster doses, against these emerging variants and subvariants, such as BA.2-derived sub-lineages, XBB sub-lineages, and BA.2.86 (Pirola). Furthermore, we discuss the latest advancements in vaccine technology, including multivalent and pan-coronavirus approaches, along with the development of several next-generation coronavirus vaccines, such as exosome-based, virus-like particle (VLP), mucosal, and nanomaterial-based vaccines. Finally, we highlight the key challenges and critical areas for future research to address the evolving threat of SARS-CoV-2 subvariants and to develop strategies for combating the emergence of new viral threats, thereby improving preparedness for future pandemics.

The antibody-mediated immune response is crucial for the development of protective immunity against SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Understanding the interaction between SARS-CoV-2 and the immune system is critical because new variants emerge as a result of the virus's ongoing evolution. Understanding the function of B cells in the SARS-CoV-2 infection process is critical for developing effective and long-lasting vaccines against this virus. Triggered by the innate immune response, B cells transform into memory B cells (MBCs). It is fascinating to observe how MBCs provide enduring immune defence, not only eradicating the infection but also safeguarding against future reinfection. If there is a lack of B cell activation or if the B cells are not functioning properly, it can lead to a serious manifestation of the disease and make immunisation less effective. Individuals with disruptions in the B cells have shown increased production of cytokines and chemokines, resulting in a poor prognosis for the disease. Therefore, we have developed an updated review article to gain insight into the involvement of B cells in SARS-CoV-2 infection. The discussion has covered the generation, functioning, and dynamics of neutralising antibodies (nAbs). Furthermore, we have emphasised immunotherapeutics that rely on nAbs.

Bioinformatics has significantly advanced RNA-based therapeutics, particularly circular RNAs (circRNAs), which outperform mRNA vaccines, by offering superior stability, sustained expression, and enhanced immunogenicity due to their covalently closed structure. This review highlights how bioinformatics and computational biology optimise circRNA vaccine design, elucidates internal ribosome entry sites (IRES) selection, open reading frame (ORF) optimisation, codon usage, RNA secondary structure prediction, and delivery system development. While circRNA vaccines may not always surpass traditional vaccines in stability, their production efficiency and therapeutic efficacy can be enhanced through computational strategies. The discussion also addresses challenges and future prospects, emphasizing the need for innovative solutions to overcome current limitations and advance circRNA vaccine applications.

Fractional doses of vaccine to protect against COVID-19 offer the potential to expand vaccine availability, reduce side effects, and enhance vaccination campaign efficiency. This study aimed to assess the immune response and safety of fractional doses of SARS-CoV-2 booster vaccines compared to full doses in immunocompetent adults aged 18-60 who had previously received a full series of Sinovac, AZD1222 (AstraZeneca), or BNT162b2 (Pfizer/BioNTech).

This trial was structured as a parallel-group, double-blind, randomised Phase IV non-inferiority study, carried out in Campo Grande, Midwest, Brazil. After obtaining consent, eligible participants were randomised to one of 5-6 study arms, depending on their priming vaccine. Participants were followed for 21-60 days after vaccination through in-person visits and remote contact for blood collection and safety evaluation. Anti-spike binding IgG antibodies were measured by ELISA. The primary outcome was the difference in seroresponse rates between the full and fractional doses, with a non-inferiority threshold of 10%.

A total of 1451 participants were randomised and administered booster vaccines between 5 July and 3 October, 2022. A half dose of BNT162b2 met the non-inferiority threshold, compared to a full dose in the Sinovac and AZD1222 primed groups. Sinovac induced an inferior response compared to AZD1222 and BNT162b2 full or fractional dose boosters in participants primed with Sinovac. Fractional booster doses of BNT162b2 consistently resulted in higher seroresponse rates (ranging from 35.4% to 78.3%) compared to fractional boosters of AZD1222 (ranging from 10.0% to 44.7%) or a full dose of Sinovac (4.2%). Both full and fractional dose vaccines were generally well tolerated. Local and systemic adverse events occurred across all treatment arms in line with expectations, with nine serious adverse events reported, none of which were determined to be related to study vaccination.

Our data show that the immunogenicity of booster vaccines depends on the initial vaccine, baseline antibody levels, and the booster vaccine used. Fractional doses of BNT162b2 and AZD1222 were non-inferior to a full Sinovac booster in individuals primed with Sinovac. However, fractional doses of BNT162b2 were not non-inferior in BNT162b2-primed individuals, and AZD1222 fractional doses were only non-inferior in the AZD1222 priming arm. We advise against Sinovac as a booster. Fractional doses of BNT162b2 or AZD1222 remain practical alternatives for Sinovac-primed populations in resource-limited settings.

Coalition for Epidemic Preparedness Innovations (CEPI)/Sabin Vaccine Institute.

The key role and impact of nanotechnology in vaccine development became particularly prominent following the outbreak of the coronavirus disease 2019 (COVID-19) pandemic in 2019. Especially in the process of designing and optimising COVID-19 vaccines, the application of nanomaterials significantly accelerated vaccine development and efficient delivery. In this review, we categorised and evaluated conventional vaccines, including attenuated live vaccines, inactivated vaccines, and subunit vaccines, highlighting their advantages and limitations. We summarised the development history, mechanisms, and latest technologies of vaccine adjuvants, emphasising their critical role in immune responses. Furthermore, we focused on the application of nanotechnology in the vaccine field, detailing the characteristics of nanoparticle vaccines, including virus-like particles, lipid-based carriers, inorganic nanoparticles, and polymer-based carriers. We emphasised their potential advantages in enhancing vaccine stability and immunogenicity, as well as their ability to deliver vaccines and present antigens through various routes. Despite facing challenges such as low drug loading efficiency, issues with long-term storage, high costs, and difficulties in large-scale production, nano-vaccines hold promise for the future. This review underscores the pivotal role and prospects of nanotechnology in vaccine development, offering new pathways and strategies to address current and future disease challenges.

Since the COVID-19 pandemic, it has caused a great threat to the global economy and public health, initiatives have been launched to control the spread of the virus. To explore the efficacy of drugs, a large number of clinical trials have been carried out, with the purpose of providing guidelines based on high-quality evidence for clinicians. We mainly discuss therapeutic agents for COVID-19 and explain the mechanism, including antiviral agents, tocilizumab, Janus kinase (JAK) inhibitors, neutralizing antibody therapies and corticosteroids. In addition, the COVID-19 vaccine has been proven to be efficacious in preventing SARS-CoV-2 infection. We systematically analyzed four mainstream vaccine platforms: messenger RNA (mRNA) vaccines, viral vector vaccines, inactivated vaccines and protein subunit vaccines. We evaluated the therapeutic effects of drugs and vaccines through enumerating the most typical clinical trials. However, the emergence of novel variants has further complicated the interpretation of the available clinical data, especially vaccines and antibody therapies. In the post-epidemic era, therapeutic agents are still the first choice for controlling the progression of disease, whereas the protective effect of vaccines against different strains should be assessed comprehensively.

Traditional vaccinology has primarily focused on neutralizing antibody titers as the main correlate of vaccine efficacy, often overlooking the multifaceted roles of antibody Fc effector functions in orchestrating protective immune responses. Fc-mediated immune responses play a pivotal role in immune modulation and pathogen clearance. Emerging evidence from natural infections and vaccine studies highlights the critical contribution of Fc effector functions in determining the quality and durability of immunity. This work explores the limitations of current vaccine evaluation paradigms that prioritize neutralization over Fc effector mechanisms. It also describes findings from a study showing an unexpected role for SARS-CoV-2 anti-spike antibodies: both convalescent plasma and patient-derived monoclonal antibodies (mAbs) lead to maximum phagocytic capacity by monocytes at low concentrations, whereas at higher concentrations the phagocytic capacity was reduced. Given that the severity of COVID-19 disease and antibody titers are strongly positively correlated, this work challenges the paradigm that high antibodies offer better protection against severe disease. It is proposed that humoral and cellular responses elicited by vaccination should never be higher than those produced by natural infection. By integrating antibody Fc effector functions into vaccine development, a paradigm shift is proposed that emphasizes synergic antibody responses. Such an approach could transform vaccine efficacy assessment, enhance protection against dangerous pathogens, and drive innovation in vaccine design.

Emerging variants of SARS-CoV-2 pose great technological and regulatory challenges to vaccine manufacturing, especially in downstream processing. To address this dilemma, the development of broad-spectrum affinity chromatography for the purification of wild-type SARS-CoV-2 and its variants is crucial. We propose a comprehensive strategy to achieve this goal via the identification of high-affinity peptides by affinity selection of phage display and next-generation sequencing (NGS) and the evaluation of chromatographic performance. Two peptides targeting the angiotensin-converting enzyme 2 (ACE2)-binding motif on the receptor-binding domain (RBD), HFVKTPARWAWG (SP-HFV) and HYRTSHWHHLLG (SP-HYR), were obtained from the most abundant sequences of the enriched phage library. They exhibited nanomolar affinity for the RBD and trimeric spike protein (Trimer S), and had broad-spectrum affinity for all the RBDs from the variants. Molecular dynamics simulations revealed the different binding regions of SP-HFV and SP-HYR in the ACE2-binding motif and key residues contributing to binding. After SP-HYR was coupled onto agarose matrices, chromatographic results showed that the RBD and Trimer S from the wild-type and Omicron variant could be adsorbed at pH 6.0-6.5 and eluted by increasing the salt concentration, exhibiting broad-spectrum and mild-elution characteristics of affinity chromatography. Finally, the affinity chromatography was applied for the purification of inactivated SARS-CoV-2 and Omicron vaccines, affording high yields (84.5-93.0 %) and purities (81.3-98.0 %), and great resistance to harsh cleaning-in-place in 20 cycles. This work clearly demonstrated the commercial potential of broad-spectrum affinity chromatography for vaccine purification to address the rapid variation of pathogenic viruses.

Following the worldwide spread of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a vital requirement for safe and effective vaccines against Coronavirus disease 2019 (COVID-19). Therefore, several vaccine-candidate platforms have been designed, tested, and developed. Based on guidelines, preclinical studies are recommended to assess the safety and potency of COVID-19 vaccines in appropriate in vitro and in vivo settings. These studies provide essential information to describe the potential toxic properties of a vaccine and the formulation of vaccine agents during the preclinical trial phase. In toxicology studies, several factors must be considered, such as the appropriate animal species and strains, dosing timetable, mode of administration, time of sampling for biochemistry and antibody evaluation, and necropsy. Pharmacokinetic/ biodistribution studies are not usually required for infectious disease prophylaxis vaccines unless the vaccine contains a novel substance. Evaluating their biodistribution is crucial for newly developed vaccines, such as lipid nanoparticles -messenger RNA (LNP-mRNA), DNA, and Viral vectors in non-replicated (VVnr), or recombinant virus vaccines. The review highlights the importance of preclinical studies in assessing the safety and efficacy of vaccine candidates. This guidance is essential for researchers and manufacturers to design effective vaccines that can progress to clinical trials safely.

The SARS-CoV-2 outbreak in late 2019 triggered a major increase in activities related to immunobiology and immunotherapy to cope with and find solutions to end the COVID-19 pandemic. The unprecedented approach to research and development of drugs and vaccines against SARS-CoV-2 has substantially improved the understanding of immunobiology for COVID-19, which can also be applied to other infectious diseases. Major efforts were dedicated to the repurposing of existing antiviral drugs and the development of novel ones. For this reason, numerous approaches to evaluating interferons, immunoglobulins, and cytokine inhibitors have been conducted. Antibody-based therapies, especially employing monoclonal antibodies have also been on the agenda. Cell-based therapies involving dendritic cells, macrophages, and CAR T-cell approaches have been evaluated. Many existing antiviral drugs have been repurposed for COVID-19 and novel formulations have been tested. The extraordinarily rapid development of efficient vaccines led to the breakthrough of novel vaccine approaches such as mRNA-based vaccines saving millions of lives. Waning immunity of existing vaccines and emerging SARS-CoV-2 variants have required additional booster vaccinations and re-engineering of new versions of COVID-19 vaccines.

To enhance the personal immunity to COVID-19, a third booster dose of inactivated COVID-19 vaccines program campaign was implemented in China. Our study endeavored to compare the dynamics of neutralizing antibodies generated by four distinct booster vaccines against three kinds of live SARS-CoV-2 virus (wild-type, Delta AY.23, and Omicron BA5.2). This cohort study involved 320 healthy individuals, who were randomly assigned to four groups, to receive boosters with inactivated vaccine (COVac and BIBP), the adenovirus type-5-vectored vaccine (Convidecia), and the recombinant protein-based vaccine (Zifivax), respectively, all the vaccines studied had the Wuhan variant as their parental variant. Participants were recruited from December 2021 to June 2022, with a follow-up period of 180 days. We evaluated humoral immune responses and their longevity by measuring the geometric mean titers (GMTs) of neutralizing antibodies against the SARS-CoV-2 virus at various time points post-boost. After 180 days of follow-up, 310 participants completed the study. Across all booster groups, neutralizing antibodies against the wild-type virus declined sharply within the first 90 days, accounting for an 81.24 to 92.34% reduction, then slowed down with gradually decreasing decay rates. By day 14 of post-boost, the ability to neutralize the Delta variant slightly diminished compared to the wild-type, whereas neutralizing antibodies against the Omicron variant exhibited a more pronounced decline, ranging from 10.78 to 19.88 times lower than those against the wild-type. Notably, heterologous boosting with the Convidecia vaccine maintained higher GMTs of neutralizing antibodies against both Delta and Omicron variants compared to the other boosters. At 180 days of post-boost, GMTs of neutralizing antibodies against SARS-CoV-2 had substantially decreased, yet individuals who received the Convidecia vaccine still exhibited higher titers than those who received other boosters. In summary, neutralizing antibody levels significantly waned 180 days after the third vaccine dose, with the most pronounced decline occurring within the initial 90 days. Heterologous boosting with Convidecia demonstrated a more robust, durable, and broad humoral immune response compared to boosting with inactivated vaccines or Zifivax, suggesting that adenovirus vector vaccines possess a special advantage in the realm of vaccine development for preventing infectious diseases.

The persistent emergence of COVID-19 variants and recurrent waves of infection worldwide underscores the urgent need for vaccines that effectively reduce viral transmission and prevent infections. Current intramuscular (IM) COVID-19 vaccines inadequately protect the upper respiratory mucosa. In response, we have developed a nonadjuvanted, IFN-armed SARS-CoV-2 fusion protein vaccine with IM priming and intranasal (IN) boost sequential immunization. Our study showed that this sequential vaccination strategy of the IM+IN significantly enhanced both upper respiratory and systemic antiviral immunity in a mouse model, characterized by the rapid increase in systemic and mucosal T and B cell responses, particularly the mucosal IgA antibody response. The IN boost triggered a swift secondary immune response, rapidly inducing antigen-specific IgA+ B cells. Further B cell receptor-seq (BCR-seq) analysis indicated that these IgA+ B cells primarily arose through direct class switching from preexisting IgG+ B cells in draining lymph nodes. Notably, our clinical studies revealed that the IN boost after IM vaccination elicited a robust systemic IgA antibody response in humans, as measured in serum. Thus, we believe that our cytokine-armed protein vaccine presents a promising strategy for inducing rapid and potent mucosal protection against respiratory viral infections.

The SARS-CoV-2 Omicron variant, since its initial detection, has rapidly spread across the globe, becoming the dominant strain. It is important to study the immune response of SARS-CoV-2 Omicron variant due to its remarkable ability to escape the majority of existing SARS-CoV-2 neutralizing antibodies. The surge in SARS-CoV-2 Omicron infections among most Chinese residents by the end of 2022 provides a unique opportunity to understand immune system's response to Omicron in populations with limited exposure to prior SARS-CoV-2 variants.

We tested the levels of IgG, IgA, and IgM specific to the prototype SARS-CoV-2 RBD (receptor-binding domain) in blood samples from 636 individuals by chemical luminescence assay, ELISA and pseudovirus-based neutralization assay.

Inoculation with inactivated prototype SARS-CoV-2 vaccines or recombinant protein vaccines showed higher IgG levels after infection than the unvaccinated individuals. Moreover, the age resulted in different IgG levels after the Omicron infection as IgG level of the patients aged > 60 years was lower than that of patients aged < 60 years. This indicates that the IgG induced by SARS-CoV-2 Omicron breakthrough infection was different between old and young individuals. We found that a booster dose of the prototype SARS-CoV-2 vaccine led to a significant increase in the neutralizing immune response against the prototype SARS-CoV-2 and helped induce neutralizing antibodies against BA.5 and BF.7 variants after an Omicron breakthrough infection in young individuals, which is different from a previous report on older people.

These data suggest that the prototype SARS-CoV-2 booster vaccination helps induce high levels of neutralizing antibodies against Omicron BA.5 and BF.7 variants after Omicron breakthrough infection in young individuals.

This study is a purely observational study.

This study describes the seroconversion and serodynamics of IgG antibodies against the RBD of SARS-CoV-2 in the general population of Sleman District, Yogyakarta Special Province. We aim to identify possible factors that correlate with the seroconversion and serodynamics of IgG antibodies against the RBD of SARS-CoV-2.

We performed a longitudinal study of the population at Health and Demographic Surveillance System (HDSS) Sleman, Yogyakarta, Indonesia. Study subjects were recruited between April and December 2021 using convenience sampling and were followed up 2 times, i.e. 4-5 and 8-9 weeks. The inclusion criteria for subjects were age ≥ 18 years, absence of flu-like symptoms, and negative COVID-19 by using GeNose C19® screening. A community-based survey on demographics, comorbidities and smoking habits were documented at baseline, while a history of vaccination, COVID-19-related symptoms, mobility, and preventive measures, weight and height as well as a venous blood draw, were collected at each visit. The anti-RBD-SARS-CoV-2 IgG antibody concentration from blood plasma was measured using chemiluminescent microplate immunoassay (CMIA). Descriptive analysis was performed based on IgG seropositivity by using chi-squared test or Fisher's exact test, as appropriate. Logistic regression was subsequently performed to identify factors that were correlated with IgG seropositivity. Further, a grouping of subjects based on IgG seropositivity was done to analyze factors that might correlate with seroconversion and serodynamics of anti-RBD-SARS-CoV-2 IgG antibody. A P value ≤ 0.05 was considered to indicate a significant difference.

Three hundred eighty-five (385) participants were analyzed. At baseline, 307 out of 385 (79.7%) subjects were seropositive for the IgG antibody against the RBD of SARS-CoV-2. Descriptive analysis showed that sex, marital status, smoking habits, obesity, vaccination status, and preventive measures were different between the IgG anti-RBD-SARS-CoV-2 seropositive and negative individuals (p≤ 0.05). Further analysis showed that, vaccination was the factor most strongly correlated with seropositivity [OR = 20.58; 95% CI 10.82, 39.15]. Based on the correlation, we separated subjects into 4 groups. Group 1 (seronegative-unvaccinated individuals; 50 subjects); Group 2 (seronegative-vaccinated individuals; 27 subjects); Group 3 (seropositive-unvaccinated individuals; 25 subjects); and Group 4 (seropositive-vaccinated individuals; 282 subjects). During monitoring, 27/49 (55.10%), 5/25 (20%), 9/22 (40.91%), and 27/257 (10.51%) of subjects in Group 1, 2, 3, and 4 respectively, received 1 or 2 doses of COVID19 vaccine. When comparing seroconversion at baseline and monitoring 2, positive IgG seroconversion was observed in Group 1 (from 0/51 (0%) to 23/49 (46.94%)) and Group 2 (from 0/27 (0%) to 10/25 (40%)), but negative seroconversion was observed in Group 4 (from 282/0 (100%) to 248/257 (96.50%)); while, all subjects in Group 3 remained seropositive at the end of monitoring. This evidence suggested for hybrid immunity, on which infection and vaccine simultaneously contributes to anti-RBD-SARS-CoV-2 IgG seroconversion.

A high seroprevalence of the IgG antibody against RBD-SARS-CoV-2 in the Sleman population was found to correlate with COVID-19 vaccination and as infection occurred, thus enhancing hybrid immunity. We also identified nonresponder and rapid antibody decaying individuals, that call for targeted vaccinations in addition to annual universal boosting.

BackgroundHuman immunodeficiency virus (HIV) cases are rising in Central Asia and Kazakhstan. People living with HIV (PLWH) in Kazakhstan are at heightened risk of severe COVID-19. We conducted a study to evaluate determinants of COVID-19 vaccine uptake among PLWH in Kazakhstan.MethodsIn this cross-sectional study, 196 PLWH were recruited from the Almaty City AIDS Center (July 2022-January 2023). We used logistic regression to evaluate how multilevel factors are associated with COVID-19 vaccine uptake among PLWH in Kazakhstan.ResultsCOVID-19 vaccine non-uptake was associated with higher HIV stigma scores (AOR = 1.08, 95%CI:1.02,1.16, P = 0.017), a lower level of education (AOR = 2.53, 95%CI: 1.04,6.17, P = 0.0412), and never receiving the flu vaccine (AOR = 15.64, 95%CI:3.66,66.89, P = 0.0002). Participants with at least mild anxiety symptoms (AOR = 0.15, 95%CI:0.03,0.64, P = 0.0107) and a positive attitude towards vaccination (AOR = 0.79, 95%CI: 0.73,0.86, P < 0.0001) were less likely to remain unvaccinated against COVID-19.ConclusionsCOVID-19 vaccination campaigns should be tailored for PLWH and incorporate stigma reduction interventions within healthcare settings.

Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete. The international consensus-based CONSORT-DEFINE (Consolidated Standards for Reporting Trials Dose-finding Extension) statement, an extension of the CONSORT statement for randomised trials, was developed to improve the reporting of EPDF trials. The CONSORT-DEFINE statement introduced 21 new items and modified 19 existing CONSORT items.This CONSORT-DEFINE Explanation and Elaboration (E&E) document provides important information to enhance understanding and facilitate the implementation of the CONSORT-DEFINE checklist. For each new or modified checklist item, we provide a detailed description and its rationale with supporting evidence, and present examples from EPDF trial reports published in peer-reviewed scientific journals. When reporting the results of EPDF trials, authors are encouraged to consult the CONSORT-DEFINE E&E document, together with the CONSORT and CONSORT-DEFINE statement papers, and adhere to their recommendations. Widespread adoption of the CONSORT-DEFINE statement is likely to enhance the reporting quality of EPDF trials, thus facilitating the peer review of such studies and their appraisal by researchers, regulators, ethics committee members, and funders.

This work is a further extension of the CONSORT-DEFINE study, which was funded by the UK Medical Research Council (MRC)-National Institute for Health and Care Research (NIHR) Methodology Research Programme (MR/T044934/1). The Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU) receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec 22/100 004), which has contributed to accelerating the advancement and successful completion of this work.

NCT04993365 (ClinicalTrials.gov).

Various novel platform technologies have been used for the development of COVID-19 vaccines. In this nested cohort study among healthcare workers in Australia and Brazil who received three different COVID-19-specific vaccines, we (a) evaluated the incidence of adverse events following immunization (AEFI); (b) compared AEFI by vaccine type, dose and country; (c) identified factors influencing the incidence of AEFI; and (d) assessed the association between reactogenicity and vaccine anti-spike IgG antibody responses. Of 1302 participants who received homologous 2-dose regimens of ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech) or CoronaVac (Sinovac), 1219 (94%) completed vaccine reaction questionnaires. Following the first vaccine dose, the incidence of any systemic reaction was higher in ChAdOx1-S recipients (374/806, 46%) compared with BNT162b2 (55/151, 36%; p = 0.02) or CoronaVac (26/262, 10%; p < 0.001) recipients. After the second vaccine dose, the incidence of any systemic reaction was higher in BNT162b2 recipients (66/151, 44%) compared with ChAdOx1-S (164/806, 20%; p < 0.001) or CoronaVac (23/262, 9%; p < 0.001) recipients. AEFI risk was higher in younger participants, females, participants in Australia, and varied by vaccine type and dose. Prior COVID-19 did not impact the risk of AEFI. Participants in Australia compared with Brazil reported a higher incidence of any local reaction (170/231, 74% vs 222/726, 31%, p < 0.001) and any systemic reaction (171/231, 74% vs 328/726, 45%, p < 0.001), regardless of vaccine type. Following a primary course of ChAdOx1-S or CoronaVac vaccination, participants who did not report AEFI seroconverted at a similar rate to those who reported local or systemic reactions. In conclusion, we found that the incidence of AEFI was influenced by participant age and COVID-19 vaccine type, and differed between participants in Australia and Brazil.

Rabies, primarily transmitted to humans by dogs (accounting for 99% of cases). Once rabies occurs, its mortality rate is approximately 100%. Post-exposure prophylaxis (PEP) is critical for preventing the onset of rabies after exposure to rabid animals, and vaccination is a pivotal element of PEP. However, high costs and complex immunization protocols have led to poor adherence to rabies vaccinations. Consequently, there is an urgent need to develop new rabies vaccines that are safe, highly immunogenic, and cost-effective to improve compliance and effectively prevent rabies. In recent years, mRNA vaccines have made significant progress in the structural modification and optimization of delivery systems. Various mRNA vaccines are currently undergoing clinical trials, positioning them as viable alternatives to the traditional rabies vaccines. In this article, we discuss a novel mRNA rabies vaccine currently undergoing clinical and preclinical testing, and evaluate its potential to replace existing vaccines.

To assess the impact of the SARS-CoV-2 booster dose on the immune response against COVID-19, we conducted a cross-sectional study in the Casablanca-Settat region of Morocco. The study included 2,802 participants from 16 provinces, all of whom had received three doses of a SARS-CoV-2 vaccine. IgG antibodies targeting the S1 RBD subunit of the SARS-CoV-2 spike protein were quantified using the SARS-CoV-2 IgG II Quant assay and measured on the Abbott Architect i2000SR instrument. Adjusted seroprevalence of anti-RBD antibodies showed that participants who received two doses of ChAdOx1-S followed by a BBIBP-CorV booster had a seroprevalence rate of 99.68% (95% CI: 99.39-99.83%), while those who received a BNT162b2 booster had a rate of 99.67% (95% CI: 99.38-99.82%). Both rates were higher than those observed with other vaccination regimens. The evaluation of booster dose effects revealed significant differences in anti-RBD antibody levels across various vaccination regimens: two doses of BBIBP-CorV compared to three doses of BBIBP-CorV (P < 0.0001), two doses of BNT162b2 versus three doses of BNT162b2 (P = 0.023), two doses of ChAdOx1-S versus two doses of ChAdOx1-S with a BNT162b2 booster (P = 0.023), and two doses of BBIBP-CorV versus two doses of BBIBP-CorV with a BNT162b2 booster (P < 0.0001). However, no significant difference was found between two doses of ChAdOx1-S and three doses of ChAdOx1-S (P = 0.23). Participants with prior SARS-CoV-2 exposure who received two doses of ChAdOx1-S followed by either a BBIBP-CorV or BNT162b2 booster showed higher levels of anti-RBD IgG antibodies (P = 0.042 and P = 0.001, respectively). Interestingly, individuals with comorbidities who received the BNT162b2 booster dose exhibited a significantly stronger humoral response (P < 0.05). In conclusion, our findings highlight the effectiveness of the BNT162b2 booster dose in eliciting a strong immune response. The high seroprevalence rates achieved with both BNT162b2 and BBIBP-CorV boosters reflect the country's robust vaccination strategy.

Background: COVID-19 became a global health crisis in early 2020, and the way out of the crisis was the rapid development of vaccines by Sinopharm, Pfizer, and Sputnik, among others, which played a crucial role in controlling the pandemic. Therefore, this study aims to investigate the long-term immune response by measuring the levels of anti-S1 IgG antibodies induced by homologous and heterologous vaccination regimens. Methods: We investigated the titer of the anti-S1 IgG antibody produced for the viral surface antigen 3, 6 months after the second dose, before the third dose, and 1, 3, and 6 months after the third dose. Results: Anti-S1 IgG antibody levels significantly increased three/six months after the second dose and following the booster in individuals without prior COVID-19 infection who received all three homologous vaccine doses. The group that initially responded poorly to Sinopharm showed a significant and sustained increase after receiving the Pfizer booster. Additionally, prior SARS-CoV-2 infection between primary and booster vaccination boosted anti-S1 antibody titers in all individuals, regardless of the vaccine used. The highest vaccine efficacy was observed during the primary vaccination period and declined over time, especially during the omicron-dominant period. Conclusions: The results suggest that while homologous and heterologous booster doses can significantly enhance anti-S1 IgG antibody levels, prior SARS-CoV-2 infection and the type of vaccine administered influence the duration and magnitude of the immune response.

Objectives: Accumulating evidence has confirmed the efficacy and safety of COVID-19 vaccines against SARS-CoV-2 infection. However, the effect of COVID-19 vaccination on immuno-virological parameters in people with HIV (PWH) is uncertain. Methods: A total of 372 PWH treated at Beijing Ditan Hospital were included. Unvaccinated PWH were matched 1:3 with vaccinated PWH using a propensity score matching algorithm. Differences in immuno-virological markers between the matched groups were analyzed. The Wilcoxon signed rank test was used to test for changes in CD4 and CD8 counts and HIV viral load over two months around vaccination. In addition, we investigated the long-term changes in HIV-related markers in different vaccination dose groups and in the entire vaccinated population. Results: Vaccinated PWH had a higher CD4/CD8 ratio (0.64 (0.49, 0.78) vs. 0.80 (0.56, 1.03), p = 0.037) than unvaccinated PWH within a two-month window after the third dose. There were 337 PWH who received COVID-19 vaccination, and 73.9% (n = 249) received three doses of vaccine. We observed a transient increase in CD4 count and CD4/CD8 ratio within a two-month window after vaccination, especially after the second dose (CD4 count: 583.5 (428.5, 706.8) vs. 618.0 (452.0, 744.0), p = 0.018; CD4/CD8 ratio: 0.70 (0.50, 0.91) vs. 0.71 (0.53, 0.96), p < 0.001)) and the third dose (CD4 count: 575.5 (435.5, 717.0) vs. 577.5 (440.8, 754.8), p = 0.001; CD4/CD8 ratio: 0.70 (0.52, 0.93) vs. 0.79 (0.53, 1.00), p < 0.001)). Recent CD4 counts and CD4/CD8 ratios were lower than after COVID-19 but remained higher than before COVID-19 in vaccinated PWH. In addition, COVID-19 vaccination had no negative effect on HIV viral load. Conclusions: A transient increase in CD4 count and CD4/CD8 ratio was observed after COVID-19 vaccination. However, the enhanced cellular immune response induced by vaccination may diminish over time and return to normal levels. There is no adverse effect of vaccination on HIV viral load.

Vaccination has emerged as the primar approach for managing the COVID-19 pandemic. Despite certain clinical trials reporting the safety and immunogenicity of CoronaVac, additional multicenter real-world studies are still necessary. In this study, we recruited 506 healthy volunteers who were not infected with COVID-19 or vaccinated. Each participant provided peripheral blood samples three times: prior to the first dose of vaccine, prior to the second dose, and 8 weeks following the second dose. Ultimately, 388 participants completed the entire follow-up process. No serious adverse events were observed among any of the participants. Within 1 week of vaccination, 13.4% of participants experienced systemic adverse reactions, with fatigue (5.93%) and dizziness (3.35%) being the most frequent. Although some clinical indicators, including creatinine, significantly changed after vaccination (p < 0.05), the mean of all altered indicators remained within the normal range. The positive rates of neutralizing antibodies (NAb), IgG, and IgM were 12.3%, 18.85%, and 5.24% prior to the second dose, respectively; and 57.99%, 86.34%, and 2.32% at 8 weeks following the second dose, respectively. Additionally, seven indicators, such as sex, age, and BMI, were significantly correlated with NAb (p < 0.05). Finally, a prediction model was developed based on age, monocytes, and alanine aminotransferase (ALT) with an AUC value of 87.56% in the train set and 80.71% in the test set. This study demonstrated that safety and immunogenicity of CoronaVac were good. The prediction model based on the baseline clinical characteristics prior to vaccination can help to develop more suitable vaccination strategies.

To investigate the safety of COVID-19 inactivated vaccine in immature mice.

We selected 3-week-old immature BALB/c mice, continuously observed until 7 weeks old after continuous immunization with fully inactivated vaccine (initial strengthening), and sacrificed BALB/c mice at 7 weeks old, and used H&E, Masson, mast cells and Ki-67 staining to analyze the changes of heart, liver, spleen, kidney, lung and brain. In addition, RNA was extracted from important organs such as the heart, liver, spleen, kidney, lung, and brain, and to evaluate whether there was any effect after vaccination through bulk-RNA sequencing.

After H&E, Masson, mast cells and Ki-67 staining analyses, there are no significant differences between tissues and organs in the vaccine group and the PBS group, and RNA-Seq did not show that the vaccine had any effect on immature mice.

COVID-19 inactivated vaccine is safe in immature mice.