ANTI-RBD IgG RESPONSE AFTER A PRIMARY ANTI-SARS-COV-2 VACCINATION COURSE WITH BNT162B2 AND AFTER A THIRD DOSE WITH A FIRST-GENERATION mRNA VACCINE IN A COHORT OF PEOPLE LIVING WITH HIV

Background Data on the immunogenicity of vaccines against SARS-CoV-2 document the reduction of the antibody titer six months after the end of the primary vaccination course and suggest the benefit of an additional vaccine dose, especially in frail and/or immunosuppressed subjects. Data on SARS-CoV-2 m-RNA vaccines immunogenicity in people living with HIV (PLWH) are currently limited, in relation to both the primary vaccination course and the boosting dose. Methods A cohort of PLWH on antiretroviral therapy attending a SARS-CoV-2 vaccination program were included prospectively after receiving a primary vaccine course with BNT162b2 and after a boosting dose with a first-generation m-RNA vaccine. Participants were stratified by baseline CD4 T-lymphocytes count (poor CD4 recovery, PCDR: <200/mm3; intermediate CD4 recovery, ICDR: 200–500/mm3; high CD4 recovery, HCDR: >500/mm3). RBD-binding IgG were measured using a commercial chemiluminescence microparticle antibody assay (Roche Elecsys® Anti-SARS-CoV-2 S) and titers were stratified in five categories: non-reactive (<5.58 BAU/mL); inconclusive (>5.58 BAU/mL and <45 BAU/mL); positive low (>45 BAU/mL and <205 BAU/mL); positive intermediate (>205 BAU/mL and <817 BAU/mL), and positive high (>817 BAU/mL). PLWH were evaluated at four successive time points: before the start of vaccination (T1), 3 weeks after the first dose (T2), 3 months + 1 month after the first dose (T3) and 1 month + 1 month after the third dose (T4). The onset of break-through infection was evaluated up to 6 months after the third vaccine dose. Results A total of 304 subjects were enrolled. Three months after the primary vaccination course with BNT162b2, 97% of 214 PLWH naïve for SARS-CoV-2 infection had a detectable antibody response, mainly at intermediate (51%) and high (35%) titers. Elicited titer was mainly positive-intermediate, for subjects both with low and with high pre-vaccinal CD4 T-lymphocyte counts (56% vs 50%). A positive-high anti-RBD IgG titer was reached especially in subjects with more than 500/mm3 CD4 T-lymphocytes at baseline in comparison to those with less than 500/mm3 (39% vs 21%). Advanced age and male gender were associated with the probability of developing a medium-low antibody titer. The presence of two or more comorbidities also seemed to be associated with a higher probability of developing a low-medium serological response. Current CD4 T-lymphocytes count greater than 500/mm3 before the administration of the first vaccine dose, was associated with an increased likelihood of developing a high serological response (OR 2.39; CI95% 1.04-5.53), but only at univariable analysis. An additional dose of SARS-CoV-2 mRNA vaccine after the initial two-dose vaccination, resulted in higher levels of immunity, both in PLWH with a baseline CD4 T-lymphocytes count higher and lower than 500/mm3 (97% vs 83%). 27% of 301 evaluable PLWH experienced at least one SARS-CoV-2 infection, mainly asymptomatic or pauci-symptomatic and at an average of 4.2 ± 3.2 months after the third booster dose (80% of infectious episodes). The probability of becoming infected after the booster was higher among SARS-CoV-2 naïve individuals (P .001). Conclusions 97% of PLWHs developed a humoral response against SARS-CoV-2 within three months after receiving a primary course with BNT162b2, albeit poorer in those with CD4 T-cell <500/mm3 versus those with >500 cell/mm3 at baseline. An additional dose of a m-RNA vaccine resulted in higher levels of immunity, independently from the baseline CD4 T-lymphocyte counts. First generation m-RNA vaccines, including booster doses, did not prevent SARS-CoV-2 infection in 27% of subjects but infective episodes were asymptomatic or pauci-symptomatic, suggesting the ability to prevent severe COVID-19 also caused by Omicron. Studies to monitor over time the humoral responses after boosting vaccination and on the immunogenicity of new bivalent omicron-containing vaccine are needed, also in PLWH.