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Arthropod-borne viruses (arboviruses) warrant attention in the global health landscape because of their potential to cause widespread epidemics worldwide (1). Epizootics in animals may signal an increase in virus activity [...]

The SARS-CoV-2 Omicron variant escapes neutralizing antibodies elicited by vaccines or infection. However, whether Omicron triggers cross-reactive humoral responses to other variants of concern (VOCs) remains unknown. We used plasma from 20 unvaccinated and 7 vaccinated individuals infected by Omicron BA.1 to test binding, Fc effector function, and neutralization against VOCs. In unvaccinated individuals, Fc effector function and binding antibodies targeted Omicron and other VOCs at comparable levels. However, Omicron BA.1-triggered neutralization was not extensively cross-reactive for VOCs (14- to 31-fold titer reduction), and we observed 4-fold decreased titers against Omicron BA.2. In contrast, vaccination followed by breakthrough Omicron infection associated with improved cross-neutralization of VOCs with titers exceeding 1:2,100. This has important implications for the vulnerability of unvaccinated Omicron-infected individuals to reinfection by circulating and emerging VOCs. Although Omicron-based immunogens might be adequate boosters, they are unlikely to be superior to existing vaccines for priming in SARS-CoV-2-naive individuals. [Display omitted] • Omicron infection elicits potent neutralizing and Fc effector antibody responses • Omicron-triggered neutralizing antibodies are poorly cross-reactive for VOCs • Vaccination prior to infection increases antibody titers and cross-reactivity • Omicron vaccines are unlikely to be superior to current vaccines in naive individuals Richardson et al. show that SARS-CoV-2 Omicron infection in unvaccinated individuals triggers potent antibody responses; however, cross-reactivity against variants of concern is poor. In contrast, Omicron BA.1 breakthrough infection in vaccinated individuals elicits high titer cross-reactive antibodies. Omicron-based vaccines are thus unlikely to be superior immunogens in SARS-COV-2-naive individuals. [ABSTRACT FROM AUTHOR]

The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern. [Display omitted] • Infection before Ad26CoV2.S vaccination boosts binding, neutralization, and ADCC • Antibody boosting is not affected by time between infection and vaccination • Neutralization breadth for VOCs is determined by the sequence of the infecting virus • T cell responses are moderately boosted by prior infection and cross-react with VOCs Keeton, Richardson, Moyo-Gwete, et al. show that SARS-CoV-2 infection prior to Ad26CoV2.S vaccination significantly boosts cross-reactive ADCC and binding and neutralizing antibodies and moderately boosts T cell responses against variants of concern. Furthermore, the infecting virus spike sequence determines the cross-reactivity of neutralizing responses, with implications for second-generation vaccine design. [ABSTRACT FROM AUTHOR]