Fuente: PubMed "nature biotechnology" BMC Med. 2025 Dec 15. doi: 10.1186/s12916-025-04535-8. Online ahead of print.ABSTRACTBACKGROUND: The Omicron lineage of SARS-CoV-2 showed a remarkable ability to escape vaccine-induced immunity. In a Phase 2 clinical trial, we investigated whether a third booster/fifth dose of one of three inactivated SARS-CoV-2 vaccine candidates, based on the Delta and Omicron BA.1 variants, enhanced humoral and cellular immune responses against SARS-CoV-2.METHODS: Volunteers who received either four doses of CoronaVac® (homologous group, n = 228) or two doses of CoronaVac® followed by two mRNA vaccine doses (heterologous group, n = 298) were randomly assigned to receive an Omicron BA.1-based, trivalent (ancestral, Delta, Omicron BA.1) inactivated vaccine or an additional dose of CoronaVac® (heterologous group only). Local and systemic adverse events were recorded for 7 days after immunization with the fifth dose. Blood samples were collected at the time of immunization (day 0), 28 days post-immunization, and 180 days post-immunization. The immune response induced by vaccination was evaluated by quantifying total IgG against SARS-CoV-2 and neutralizing antibodies, IgG-producing B cells, relative antibody avidity, SARS-CoV-2-specific CD4+ and CD8+ T cells, and IFN-γ-producing cells.RESULTS: The most common local adverse event was pain at the site of inoculation (deltoid area), reported in 43.2% of the participants. No severe adverse events related to vaccination were recorded. Increased SARS-CoV-2-specific IgGs were observed exclusively in the homologous group at 28 days post-vaccination compared to the pre-immune status. Reduced neutralizing antibodies against the Omicron BA.1 variant were detected in both groups when compared to the ancestral (WT) virus, and no changes in IgG-producing B cells or relative antibody avidity were observed after vaccination. Furthermore, we observed sustained IFN-γ production and the frequency of SARS-CoV-2-specific CD4+ and CD8+ T cells before and after vaccination.CONCLUSIONS: Previous immunizations targeting the WT SARS-CoV-2 virus have induced a robust humoral and cellular response in the population, which is sustained by a fifth dose targeting either the Omicron BA.1, Delta, or WT virus.TRIAL REGISTRATION: No. NCT05593042.PMID:41398275 | DOI:10.1186/s12916-025-04535-8