tetano
Editor, Senior Moderator
Nat Commun
. 2025 Jun 25;16(1):5390.
doi: 10.1038/s41467-025-60885-0. Coordinated early immune response in the lungs is required for effective control of SARS-CoV-2 replication
Klara Lenart[SUP] 1 2 3 4 [/SUP], Hendrik Feuerstein[SUP] 1 2 3 [/SUP], Mariana Prado Marmorato[SUP] 1 2 3 [/SUP], Laura Perez Vidakovics[SUP] 5 [/SUP], Gerald McInerney[SUP] 5 [/SUP], Mimi Guebre-Xabier[SUP] 6 [/SUP], Jessica F Trost[SUP] 6 [/SUP], Bengt Eriksson[SUP] 7 [/SUP], Gale Smith[SUP] 6 [/SUP], Nita Patel[SUP] 6 [/SUP], Karin Loré[SUP] 8 9 10 [/SUP]
Affiliations
Despite waning of virus-neutralizing antibodies, protection against severe SARS-CoV-2 in the majority of immune individuals remains high, but the underlying immune mechanisms are incompletely understood. Here, rhesus macaques with pre-existing immunity from Novavax WA-1 and/or P.1 vaccines and WA-1 or P.1 infection are immunized with a bivalent WA-1/Omicron BA.5 Novavax vaccine ten months after the last exposure. The boost vaccination primarily increases the frequency of cross-reactive spike (S)-specific antibodies and B cells instead of inducing de novo BA.5-specific responses. Reinfection with heterologous Omicron XBB.1.5 six months after the boost vaccination results in low levels of virus replication in the respiratory tract compared with virus-naïve results from other studies. Whereas systemic S-specific immunity remains largely unchanged in all animals, the animals with complete protection from infection exhibit a stronger influx of S-specific IgG, monocytes, B cells and T cells into the bronchioalveolar space combined with expansion of CD69[SUP]+[/SUP]CD103[SUP]+[/SUP] lung tissue-resident, S-specific CD8 T cells compared to actively infected animals. Our results underscore the importance of localized respiratory immune responses in mediating protection from Omicron reinfection and provide guidance for future vaccine development.
. 2025 Jun 25;16(1):5390.
doi: 10.1038/s41467-025-60885-0. Coordinated early immune response in the lungs is required for effective control of SARS-CoV-2 replication
Klara Lenart[SUP] 1 2 3 4 [/SUP], Hendrik Feuerstein[SUP] 1 2 3 [/SUP], Mariana Prado Marmorato[SUP] 1 2 3 [/SUP], Laura Perez Vidakovics[SUP] 5 [/SUP], Gerald McInerney[SUP] 5 [/SUP], Mimi Guebre-Xabier[SUP] 6 [/SUP], Jessica F Trost[SUP] 6 [/SUP], Bengt Eriksson[SUP] 7 [/SUP], Gale Smith[SUP] 6 [/SUP], Nita Patel[SUP] 6 [/SUP], Karin Loré[SUP] 8 9 10 [/SUP]
Affiliations
- PMID: 40562777
- PMCID: PMC12198374
- DOI: 10.1038/s41467-025-60885-0
Despite waning of virus-neutralizing antibodies, protection against severe SARS-CoV-2 in the majority of immune individuals remains high, but the underlying immune mechanisms are incompletely understood. Here, rhesus macaques with pre-existing immunity from Novavax WA-1 and/or P.1 vaccines and WA-1 or P.1 infection are immunized with a bivalent WA-1/Omicron BA.5 Novavax vaccine ten months after the last exposure. The boost vaccination primarily increases the frequency of cross-reactive spike (S)-specific antibodies and B cells instead of inducing de novo BA.5-specific responses. Reinfection with heterologous Omicron XBB.1.5 six months after the boost vaccination results in low levels of virus replication in the respiratory tract compared with virus-naïve results from other studies. Whereas systemic S-specific immunity remains largely unchanged in all animals, the animals with complete protection from infection exhibit a stronger influx of S-specific IgG, monocytes, B cells and T cells into the bronchioalveolar space combined with expansion of CD69[SUP]+[/SUP]CD103[SUP]+[/SUP] lung tissue-resident, S-specific CD8 T cells compared to actively infected animals. Our results underscore the importance of localized respiratory immune responses in mediating protection from Omicron reinfection and provide guidance for future vaccine development.