Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10-9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42-0.93, P = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation.

Magnitude of Mycobacterium tuberculosis Infection and Its Resistance to Rifampicin Using Xpert-MTB/RIF Assay Among Presumptive Tuberculosis Patients at Motta General Hospital, Northwest Ethiopia.

BACKGROUND: Mycobacterium Tuberculosis (MTB) and its drug resistance form are the devastating infectious diseases in the world. It is the major cause of morbidity and mortality in low-income countries with Ethiopia carrying a heavy burden. Data on the magnitude of MTB and rifampicin resistance using Xpert- MTB/RIF assay is limited in the study area. Therefore, this study aimed to assess the prevalence of Mycobacterium tuberculosis and rifampicin resistance among presumptive TB patients using GeneXpert at Motta General Hospital, North West Ethiopia. METHODS: A retrospective cross-sectional study was conducted from 1st October to 30 November 2020 among patients tested for GeneXpert at Motta General Hospital, Northwest Ethiopia. Data recorded on GeneXpert test results were collected on laboratory registration book in Microbiology laboratory. Data were analyzed by using the Statistical Package for Social Sciences (SPSS) version 20. RESULTS: A total of 4109 specimens were tested using the GeneXpert automated system. Of these, the majority 2148 (52.3%) of participants were males and 1961 (47.7%) were females. Similarly, about 1553 (37.8%) were in the age range of 25-44 years followed by 1347 (32.8%) in 45-64 years. Moreover, about 2486 (60.5%) participants were from rural. The overall prevalence of M. tuberculosis was 346 (8.4%) among these, the majority 222 (5.4%) had unknown HIV status, 48 (1.2%) were HIV positive, and 314 (7.6%) was new MTB cases. The overall prevalence of rifampicin resistance was 15 (4.3%) and 8(1.7%) were intermediate. Among rifampicin resistance, 10 (2.9%) were males, 8(2.3%) lived in rural, 9 (2.6%) had unknown HIV status, 13 (3.8%) were new TB patients, and 13 (3.8%) had pulmonary tuberculosis. CONCLUSION: The prevalence of M. tuberculosis was 8.4% and relatively higher rate of rifampicin-resistant M. tuberculosis was found.