HLA-A*03:01 significantly predicts strong humoral response at six months after mRNA vaccination: Results from the observational prospective cohort study RENAISSANCE

ABSTRACT

While several studies have been conducted on HLA and Covid-19 infection, few investigated the role of HLA polymorphism on vaccination response. We previously analyzed the HLA allele and haplotype frequencies in a hundred weak responders (antibody levels <5th percentile) after mRNA anti-Covid vaccine and found some suggestions about specific alleles and one haplotype. We moved on typing individuals enrolled in the same cohort study ("RENAISSANCE") with antibody titers above the 95th percentile at six months after vaccination, in order to search for any alleles predictive of strong humoral response. Individuals with clinical history of COVID-19 or positive anti-nucleocapsid antibodies were excluded. Allelic frequencies were compared with those of weak responders and of the general population, taken from the national bone marrow donor registry, IBMDR. N = 123 evaluable individuals presented with >95th percentile antibody titers at six months after BNT162b2 vaccine. One-third of them had >2080 BAU/mL, lowest value was 1261 BAU/mL. Comparison of allelic frequencies with weak responders showed a significant different proportion of individuals carrying A*0301, A*2402 and DRB1*1601 (21.5% vs. 3.6%, 7.7% vs. 14.9% and 3.2% vs. 8.1% respectively). Moreover, when looking at alleles of the ancestral haplotype A3-B35-C4-DR1, we observed frequencies of 4.47%, 0.84% and 0% in the present cohort, IBMDR and weak responders, respectively. After adjusting for age, gender and BMI, the presence of A*0301 confirmed to be statistically significant (p<0.0001) and was predictive of high antibody titers at six months with an odds ratio of 12.5 with respect to weak antibody levels. Age was the only other significant variable, with an odds ratio of 0.96. Clinical collection data is underway to correlate Covid-19 infection rates in both cohorts, in an attempt to find a definite correlation between HLA and vaccine protection.