Summary Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with resistance to neutralizing antibodies are threatening to undermine vaccine efficacy. Vaccination and infection have led to widespread humoral immunity against the pandemic founder (Wu-Hu-1). Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet clear whether heterotypic boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. We show, in macaques immunized with Wu-Hu-1 spike, that a single dose of adjuvanted beta variant receptor binding domain (RBD) protein broadens neutralizing antibody responses to heterologous VOCs. Passive transfer of plasma sampled after Wu-Hu-1 spike immunization only partially protects K18-hACE2 mice from lethal challenge with a beta variant isolate, whereas plasma sampled following heterotypic RBD boost protects completely against disease. Graphical abstract Highlights • Heterotypic RBD boost elicits cross-neutralizing antibody responses in macaques • No evidence that original antigenic sin hinders booster immunizations with beta RBD • Pre-boost plasma only partially protects K18-hACE2 mice from beta variant challenge • Post-boost plasma affords full protection from beta variant challenge The emergence and spread of antibody-resistant SARS-CoV-2 variants of concern (VOCs) threatens to diminish vaccine efficacy. Sheward et al. show, in rhesus macaques and K18-hACE2 mice, that reduced vaccine protection against VOCs can be restored by broadening antibody responses with a third, heterotypic RBD booster immunization.
【저자키워드】 passive immunization, SARS-CoV-2, Vaccines, variants of concern, K18-hACE2 mice, original antigenic sin, heterotypic boost, animal challenge, 【초록키워드】 neutralizing antibody, Efficacy, Vaccine, pandemic, VoC, Antibody Response, variant, SARS-CoV-2 variant, Infection, outcome, immunization, Receptor binding domain, Spread, Protein, Humoral immunity, RBD, response, VOCs, antigens, plasma, macaque, Beta variant, disease, Critical, Neutralizing antibody response, Heterologous, booster, boost, single dose, rhesus macaque, Evidence, passive transfer, Abstract, antigenic, widespread, Cell, immunized, memory B, PROTECT, subsequent, reduced, elicit, restored, Against, cross-neutralizing antibody response, Heterotypic, 【제목키워드】 SARS-CoV-2 variant, animal model, RBD, Beta, boost,