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.