The relationship between genetics and infectious diseases is important in shaping our understanding of disease susceptibility, progression, and treatment. Recent research shows the impact of genetic variations, such as heme-oxygenase promoter length, on diseases like malaria and sepsis, revealing both protective and inconclusive effects. Studies on vaccine responses highlight genetic markers like human leukocyte antigens, emphasizing the potential for personalized immunization strategies. The ongoing battle against drug-resistant tuberculosis (TB) illustrates the complexity of genomic variants in predicting resistance, highlighting the need for integrated diagnostic tools. Additionally, genome-wide association studies reveal antibiotic resistance mechanisms in bacterial genomes, while host genetic polymorphisms, such as those in solute carrier family 11 member 1 and vitamin D receptor, demonstrate their role in TB susceptibility. Advanced techniques like metagenomic next-generation sequencing promise detailed pathogen detection but face challenges in cost and accessibility. A case report involving a highly virulent Mycobacterium TB strain with the pks1 gene further highlights the need for genetic insights in understanding disease severity and developing targeted interventions. This evolving landscape emphasizes the role of genetics in infectious diseases, while also addressing the need for standardized studies and accessible technologies.

Measles immunization is a cornerstone in public health, yet vaccine failure affects up to 10 % of the population, leaving some vaccinated individuals susceptible to infection. Many factors influence vaccine responses, and we hypothesize that host genetic factors impact vaccine response to measles, mumps, and rubella (MMR) vaccination.

We performed Human Leukocyte Antigen (HLA) associations and a genome-wide association study of measles plaque reduction neutralization test (PRNT) and Immunoglobin G (IgG) in 607 infants from a randomized, double-blind vaccine trial of the MMR vaccine. We examined HLA and Single Nucleotide Polymorphism (SNP) associations with measles vaccine response at 5-7 months and again at 15 months. Association analyses for SNPs were performed using linear and logistic regression, while HLA associations only utilized linear regression.

Two novel regions associated with post-vaccine measles PRNT levels were identified - one on chromosome 1 and one on chromosome 9. The most significant SNP at chromosome 9 is the intronic SNP rs77498152 within the LINGO2-gene (p-value = 1.1∙10-9), and on chromosome 1, the intronic SNP rs3005891 (p-value = 2.2∙10-8) in the LOC124904186 gene. Associations of 4-digit HLA type alleles and measles PRNT revealed the HLA-A*2902 (p = 0.006) and measles IgG HLA-B*1801 (p = 0.0025) as the most strongly associated HLA types; both were associated with a lower response.

In an MMR vaccine trial, this study identified novel genetic regions on chromosomes 1 and 9 associated with measles PRNT in healthy infants. Four-digit HLA types were associated with both Measles IgG and PRNT. Associations between SNPs and HLA have been investigated previously, and we suspect the difference in results is due to dissimilarities between cohorts and study design, especially regarding participants' age and time from immunization to immune outcome measurement.

Measles vaccination has greatly reduced the disease burden worldwide, but challenges remain due to variations in vaccine effectiveness across age groups. This study aimed to assess the serological profile of measles antibodies across different age groups, evaluate the impact of maternal immunity on antibody levels in infants under 12 months, and assess measles immunity in vaccinated individuals.

This cross-sectional study was conducted from June 2022 to January 2023 at the Children's Medical Center, a referral hospital in Iran. Serum samples were tested for measles-specific IgG and IgM antibodies using a commercial enzyme-linked immunosorbent assay (ELSA). An avidity assay was performed to assess measles virus-specific IgG antibodies on the samples that were positive and borderline for the measles IgG ELISA.

The study included 969 participants across various age groups. Among them, 23% (221 out of 953) tested positive for measles IgM ELISA, and 52% (504 out of 969) for measles IgG ELISA. Regarding the avidity assay for measles virus-specific IgG, the majority (418 out of 573, 73%) showed high-avidity antibodies. Measles-specific IgG levels varied significantly across different age groups, with infants below 6 months old showing a mean IgG level of 477 mIU/mL, declining to 230 mIU/mL between 6 and 12 months, and increasing significantly to 683 mIU/mL in the 12 to 18 month age group, reaching a peak at 938 mIU/mL among children aged 18-72 months.

The increasing IgM positivity among young Iranians suggests a rising risk of measles outbreaks, possibly due to vaccination gaps. Inadequate antibody levels in infants raise concerns about vaccination effectiveness. Considering declining maternal antibodies, vaccinating infants at 6-9 months could be beneficial. Boosters for adolescents and women may further mitigate outbreak risks.

Mycobacterium tuberculosis (M.tb.) infection leads to over 1.5 million deaths annually, despite widespread vaccination with BCG at birth. Causes for the ongoing tuberculosis endemic are complex and include the failure of BCG to protect many against progressive pulmonary disease. Host genetics is one of the known factors implicated in susceptibility to primary tuberculosis, but less is known about the role that host genetics plays in controlling host responses to vaccination against M.tb. Here, we addressed this gap by utilizing Diversity Outbred (DO) mice as a small animal model to query genetic drivers of vaccine-induced protection against M.tb. DO mice are a highly genetically and phenotypically diverse outbred population that is well suited for fine genetic mapping. Similar to outcomes in people, our previous studies demonstrated that DO mice have a wide range of disease outcomes following BCG vaccination and M.tb. challenge. In the current study, we used a large population of BCG-vaccinated/M.tb.-challenged mice to perform quantitative trait loci mapping of complex infection traits; these included lung and spleen M.tb. burdens, as well as lung cytokines measured at necropsy. We found sixteen chromosomal loci associated with complex infection traits and cytokine production. QTL associated with bacterial burdens included a region encoding major histocompatibility antigens that are known to affect susceptibility to tuberculosis, supporting validity of the approach. Most of the other QTL represent novel associations with immune responses to M.tb. and novel pathways of cytokine regulation. Most importantly, we discovered that protection induced by BCG is a multigenic trait, in which genetic loci harboring functionally-distinct candidate genes influence different aspects of immune responses that are crucial collectively for successful protection. These data provide exciting new avenues to explore and exploit in developing new vaccines against M.tb.