This systematic and meta-analysis aims to evaluate humoral and cellular responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine among kidney transplant recipients (KTRs). We conducted a systematic literature search across databases to evaluate seroconversion and cellular response rates in KTRs receiving SARS-CoV-2 vaccines. We extracted studies that assessed seroconversion rates described as the presence of antibody de novo positivity in KTRs following SARS-CoV-2 vaccination published up to January 23rd, 2022. We also performed meta-regression based on immunosuppression therapy used. A total of 44 studies involving 5,892 KTRs were included in this meta-analysis. The overall seroconversion rate following complete dose of vaccines was 39.2% (95% confidence interval [CI], 33.3%-45.3%) and cellular response rate was 41.6% (95% CI, 30.0%-53.6%). Meta-regression revealed that low antibody response rate was significantly associated with the high prevalence of mycophenolate mofetil/mycophenolic acid (p=0.04), belatacept (p=0.02), and anti-CD25 induction therapy uses (p=0.04). Conversely, tacrolimus use was associated with higher antibody response (p=0.01). This meta-analysis suggests that postvaccination seroconversion and cellular response rates in KTRs are still low. And seroconversion rate was correlated with the type of immunosuppressive agent and induction therapy used. Additional doses of the SARS-CoV-2 vaccine for this population using a different type of vaccine are considered.

COVID-19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS-CoV-2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer-BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS-CoV-2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti-spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17-2.69]), high-dose corticosteroids in the last 12 months (1.3 [1.09-1.86]), maintenance with triple immunosuppression (1.43 [1.06-2.15]), and regimen that includes mycophenolate (1.47 [1.26-2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID-19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.

The effect of the Toll-like receptor 7 agonist imiquimod before intradermal (ID) or intramuscular (IM) influenza vaccine in immunocompromised hosts is unknown.

In this open-label randomized controlled trial, kidney transplant recipients (KT) and people living with HIV (PLWH) were randomized to receive IM trivalent inactivated influenza vaccine alone (IM), IM vaccine after topical imiquimod (imi+IM) or ID vaccine after topical imiquimod (imi+ID). Immunogenicity was assessed by hemagglutination inhibition assay. The primary outcome was vaccine response, defined as seroconversion to at least one viral strain at day 21.

Seventy patients (35 KT and 35 PLWH) received IM (24), imi+IM (22), or imi+ID (24) vaccine. Vaccine response was 61% (14/23) with IM, 59% (13/22) with imi+IM, and 65% (15/23) with imi+ID vaccine (P = 0.909). Vaccine response was associated with HIV infection compared to kidney transplantation (adjusted-OR 3.74, 95% CI 1.25 - 11.23, P = 0.019), but not with imiquimod application nor ID injection. After vaccination, seroprotection to all viral strains was 79% (19/24) with IM, 68% (15/22) with imi+IM, and 70% (16/23) with imi+ID (P = 0.657). We did not observe any vaccine-related severe adverse event.

In our study, topical imiquimod did not improve the immunogenicity of influenza vaccine in KT and in PLWH.

Influenza infection poses significant risk for solid organ transplant recipients who often experience more severe infection with increased rates of complications, including those relating to the allograft. Although symptoms of influenza experienced by transplant recipients are similar to that of the general population, fever is not a ubiquitous symptom and lymphopenia is common. Annual inactivated influenza vaccine is recommended for all transplant recipients. Newer strategies such as using a higher dose vaccine or multiple doses in the same season appear to provide greater immunogenicity. Neuraminidase inhibitors are the mainstay of treatment and chemoprophylaxis although resistance may occur in the transplant setting. Influenza therapeutics are advancing, including the recent licensure of baloxavir; however, many remain to be evaluated in transplant recipients and are not yet in routine clinical use. Further population-based studies spanning multiple influenza seasons are needed to enhance our understanding of influenza epidemiology in solid organ transplant recipients. Specific assessment of newer influenza therapeutics in transplant recipients and refinement of prevention strategies are vital to reducing morbidity and mortality.

Vaccine preventable diseases account for a significant proportion of morbidity and mortality in transplant recipients and cause adverse outcomes to the patient and allograft. Patients should be screened for vaccination history at the time of pre-transplant evaluation and vaccinated at least four weeks prior to transplantation. For non-immune patients, dead-vaccines can be administered starting at six months post-transplant. Live attenuated vaccines are contraindicated after transplant due to concern for infectious complications from the vaccine and every effort should be made to vaccinate prior to transplant. Since transplant recipients are on life-long immunosuppression, these patients may have lower rates of serological conversion, lower mean antibody titers and waning of protective immunity over shorter period as compared to general population. Recommendations regarding booster dose in kidney transplant recipients with sub-optimal serological response are lacking. Travel plans should be part of routine post-transplant assessment and pre-travel vaccines and counseling should be provided. More studies are needed on vaccination schedules, serological response, need for booster doses and safety of live attenuated vaccines in this special population.

Traditionally, immune response to influenza vaccines has been measured using the haemagglutination inhibition (HAI) assay. A broader repertoire of techniques including the sensitive viral microneutralization (VMN) assay is now recommended by the European Medicines Agency (EMA). Comparing HAI and VMN, we determined immune response to a trivalent 2015-2016 seasonal inactivated influenza vaccine (SIIV) administered to 28 recipients of allogeneic haematopoietic stem cell transplant (HSCT). Vaccination was within the first-year post-transplant at a median of 78.5 (24-363) days. The proportion of patients with baseline and post-vaccination HAI titres ≥ 1:40 were 28.6% and 25% for A(H1N1)pdm09, 14.3% at both timepoints for A(H3N2), and 32.1% and 25% for B(Phuket). Pre and Post-vaccination geometric mean titres(GMT) were higher by VMN than HAI for A(H1N1)pdm09 and A(H3N2), but lower for B(Phuket)(p=<0.05). Geometric mean ratios(GMR) of baseline and post-vaccination titres were similar by HAI and VMN(p > 0.05) for all components. A single seroconversion to A(H1N1) was detected by ELISA-VMN. None of patient age, lymphocyte count, days from transplant to vaccination, donor type, or graft-versus-host disease (GVHD) or immunosuppressive therapy (IST) at vaccination correlated with baseline or post-vaccination titres by either assay. This absence of seroresponse to SIIV in the first-year post HSCT highlights the need for novel immunogenic vaccination formulations and schedules in this high-risk population.

This article discusses the recommended vaccines used before and after solid organ transplant period, including data regarding vaccine safety and efficacy and travel-related vaccines. Vaccination is an important part of the preparation for solid organ transplantation, because vaccine-preventable diseases contribute to the morbidity and mortality of these patients. A pretransplantation protocol should be encouraged in every transplant center. The main goal of vaccination is to provide seroprotection before transplantation, because iatrogenically immunosuppressed patients posttransplant have a lower seroresponse to vaccines.

Immunocompromised persons are at high risk of complications from influenza infection. This population includes those with solid organ transplants, hematopoietic stem cell transplants, solid cancers and hematologic malignancy as well as those with autoimmune conditions receiving biologic therapies. In this review, we discuss the impact of influenza infection and evidence for vaccine effectiveness and immunogenicity. Overall, lower respiratory disease from influenza is common; however, vaccine immunogenicity is low. Despite this, in some populations, influenza vaccine has demonstrated effectiveness in reducing severe disease. Various strategies to improve influenza vaccine immunogenicity have been attempted including two vaccine doses in the same influenza season, intradermal, adjuvanted, and high-dose vaccines. The timing of influenza vaccine is also important to achieve optimal immunogenicity. Given the suboptimal immunogenicity, family members and healthcare professionals involved in the care of these populations should be vaccinated. Health care professional recommendation for vaccination is an important factor in vaccine coverage.

Clinical guidelines recommend vaccinations for solid-organ transplant recipients. However, concern exists that vaccination may stimulate adverse alloimmune responses.

We systematically reviewed the published literature regarding this aspect of vaccine safety. Electronic databases were searched for interventional and observational studies assessing de novo donor-specific antibodies (DSA) and rejection episodes after vaccination against infectious pathogens. Graft loss was also assessed. A meta-analysis was conducted for prospective, controlled studies. PRISMA reporting guidelines were followed.

Ninety studies (15,645 vaccinated patients and 42,924 control patients) were included. Twelve studies included control groups. The incidence of de novo DSA (14 studies) was 23 of 1,244 patients (1.85%) at 21 to 94 days. The incidence of rejection (83 studies) was 107 episodes in 5,116 patients (2.1%) at 0.7 to 6 months. Meta-analysis of prospective controlled studies (n = 8) showed no increased rejection risk with vaccination compared with no vaccination (RR 1.12, 95% CI 0.75 to 1.70). This finding was supported by data from 3 registry analyses.

Although the current evidence lacks high-quality, controlled studies, the currently available data provide reassurance that clinicians should recommend appropriate vaccination for their transplant patients as the risk of de novo DSA and rejection is relatively low.

We analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globulins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients.

71 kidney and heart transplant recipients (basiliximab [n=43] and ATG [n=28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-γ ELISpot assays and intracellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot.

Median time of vaccination from transplantation was 29 months (IQR 8-73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group (p=0.44, p=0.61, and p=0.21, respectively). The number of influenza-specific IFN-γ-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/10(6) PBMC, p=0.0007), but no differences between treatment groups were observed (p=0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p=0.94; H3N2 p=0.34; B, p=0.79), irrespective of the type of anti-T-cell therapy.

After influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG.

Immunosuppressive treatments increase the life-long risk of solid organ transplant (SOT) recipients for severe infections, some of which are vaccine-preventable. In this review of the literature published during the last 15 months, we critically summarize vaccine-oriented articles in SOT candidates or recipients. Because of previously reported differences, vaccine-specific studies are needed for each type of SOT recipients.

Thanks to new data gathered during the H1N1/2009 influenza pandemic, recent research mainly focused on influenza vaccination, especially in kidney transplantation. Lung transplantation, mycophenolate treatment, increasing age and end-stage organ failure were frequently identified as risk factors for nonresponse to immunization in general. New evidence concerning the safety of immunizing SOT recipients with live-attenuated vaccines is obtained.

During this last year, more encouraging data have been published regarding safety and immunogenicity of vaccination in SOT recipients. New inventive strategies should be studied to overcome missed opportunities for vaccinating SOT candidates and recipients, and to promote the most effective vaccination schedule and follow-up.

Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on antigraft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti-HLA antibodies were measured before and 4-8 weeks after influenza vaccination using a solid-phase assay. Overall, 169 SOT recipients were included (kidney = 136, lung = 26, liver = 3, and combined = 4). Five (2.9%) of 169 patients developed de novo anti-HLA antibodies after vaccination, including one patient who developed donor-specific antibodies (DSA) 8 months after vaccination. In patients with pre-existing anti-HLA antibodies, median MFI was not significantly different before and after vaccination (P = 0.73 for class I and P = 0.20 for class II anti-HLA antibodies) and no development of de novo DSA was observed. Five episodes of rejection (2.9%) were observed within 12 months after vaccination, and only one patient had de novo anti-HLA antibodies. The incidence of development of anti-HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients.