SARS-CoV-2 vaccine(The Scientific and Technological Research Council of Turkey)

Incompletely resolved immune dysfunction in people living with HIV (PLWH) on antiretroviral treatment (ART) could differentially impact the CD4+ and CD8+ T cell subsets. In this study, we investigated SARS-CoV-2 vaccine-induced CD4+ and CD8+ T cell responses in 26 PLWH on ART following third-dose mRNA vaccination. Spike-specific CD4+ and CD8+ T cell responses were assessed based on the expression of activation markers, CD137/OX40 and CD137/CD25, respectively, in response to stimulation with overlapping peptides spanning the spike protein. All participants showed spike-specific T cell responses, with CD8+ responses at a higher median frequency than CD4+. Interestingly, 5 participants who showed a higher frequency of spike-specific CD4+, relative to CD8+ T cells, were significantly younger and had higher CD4 counts pre-ART, in comparison to other participants. Further multivariate analysis revealed that only CD4 count pre-ART was an important predictor of elevated spike-specific CD4+ T cell responses; however, no association was observed with neutralizing antibody (nAb) potency towards a SARS-CoV-2 spike. Our results highlight the heterogeneous immune functionality of vaccine-induced, SARS-CoV-2 spike-specific CD4+ and CD8+ T cells in PLHW on ART.

Infection with SARS-CoV-2 variants typically confers protective humoral immunity. Yet, the Omicron variant demonstrates a considerable capacity to evade immune responses in individuals previously infected with other SARS-CoV-2 strains. This has prompted investigation into Omicron’s potential resistance to neutralizing antibodies elicited by natural infection or vaccination. Importantly, the molecular mechanisms underlying this cross-protection have been investigated; however, they are not yet fully elucidated. In this study, we investigated the neutralization capacity of convalescent sera from COVID-19 patients in Córdoba City, Argentina, offering insights into immune responses against various SARS-CoV-2 variants. We analyzed samples from hospitalized patients infected with the Lambda and Gamma variants during the pandemic’s second wave from May to August 2021. These patients showed strong neutralization against Gamma, moderate activity against the B.1 and Delta variants, a weak response to Omicron BA.2, and extremely poor cross-neutralization against the Omicron BA.1.1 and BA.5 subvariants. Additionally, we examined convalescent sera from ambulatory patients during the fourth COVID-19 wave, from May to July 2022, when various Omicron variants predominated. Consistent with the hospitalized cohort, the highest neutralizing activity was observed against the Gamma variant, with moderate responses against B.1 and Delta, and low activity against Omicron subvariants. These findings highlight the critical need for region-specific studies of neutralizing responses to inform the development of future SARS-CoV-2 vaccine formulations.

Investigating the neutralizing capacity of sera obtained from COVID-19 patients infected with distinct viral variants—in this case, a comparison between pre-Omicron and Omicron strains—is essential for elucidating mechanisms of immune evasion, cross-protective immunity, and the efficacy of vaccines. Variations in neutralization profiles provide critical insights that inform the development of updated vaccines and booster immunization strategies, particularly given the pronounced immune escape characteristics exhibited by the Omicron variant. Furthermore, it is imperative to examine geographic heterogeneity, as regional differences in variant prevalence, vaccine types, and public health interventions contribute to diverse immune profiles. Conducting such investigations is critical for informing the development of tailored public health policies, facilitating the identification of immunological susceptibilities and resilience within distinct populations. This understanding is essential for improving preparedness in response to the emergence of new SARS-CoV-2 variants.