Impaired neutralizing antibody responses against the BA1.1, BA.2, and BA.5 Omicron SARS-CoV-2 subvariants in hospitalized adults infected with pre-Omicron variants in Argentina

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.IMPORTANCEInvestigating 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.