Neutralization against Omicron subvariants after BA.5/BF.7 breakthrough infection weakened as virus evolution and aging despite repeated prototype-based vaccination ¹

Abstract

Background: Omicron had swept the mainland China between December 2022 and January 2023, while SARS-CoV-2 still continued to evolve. To fully prepare for the next wave, it’s urgent to evaluate the humoral immune response post BA.5/BF.7 breakthrough infection against predominant sub-lineages among existing vaccination strategies and the elders. Method: This study enrolled a longitudinal young-adult cohort from 2/3-dose vaccination to 1 month after breakthrough infection, and an elder cohort at 1 month after breakthrough infection. Seral samples were collected and tested for humoral immune response to SARS-CoV-2 subvariants including WT, BA.2, BA.5, BF.7, BQ.1.1, CH.1.1, XBB.1.5. Results: BA.5/BF.7 breakthrough infection induced higher neutralization activity than solely vaccination in all SARS-CoV-2 strains, while the latest Omicron subvariants, BQ.1.1, CH.1.1, XBB.1.5, exhibited the strongest neutralization evasion ability. There was a negative correlation between age and humoral immune response in WT, BA.5, BQ.1.1, and XBB.1.5. Compared to non-vaccination groups, breakthrough infection in two-dose vaccination groups had significantly higher neutralizing antibody against WT, BA.2, BA.5, BF.7 but not to BQ.1.1, CH.1.1, XBB.1.5 while booster dose against the prototype prior-breakthrough would not further significantly enhance individual’s humoral responses against the latest Omicron subvariants. Conclusions: Newer variants manifest increasing immune evasion from neutralization and repeated prototype-based booster vaccines may not further enhance neutralizing antibody against emerging new variants. Older adults have lower levels of neutralizing antibody. Future vaccination strategies should aim to enhance effective neutralization to contemporary variants.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China

“…What's more, due to relatively poor immunogenicity, 44,45 the immune imprinting induced by WT inactivated vaccines may be weaker than others after Omicron subvariants reinfection, which can explain the higher NAbs against Omicron subvariants in homologous vaccinated group. Different from the documented study, 30 we find that the age has a slight effect on antibody response after Omicron BA.5 BTI and shows no influence on antibody response after XBB reinfection, revealing that muti‐antigen exposure may gradually alleviate the difference between ages. Also, we confirmed the result that elderly people with comorbidities of hypertension and cerebral apoplexy had lower antibody responses than others 46,47 .…”

“…Consistent with the previous studies, 30,38–40 our findings confirm that the NAb titers against Omicron XBB.1.5 and BA.2.86 that elicited by Omicron BA.5 BTI are remained at low levels and are not able to provide enough protection against subsequent Omicron XBB reinfection. Importantly, our results and others both demonstrate that Omicron XBB reinfection enhances the neutralizing ability against all measured Omicron subvariants, 6,32 revealing that Omicron subvariants reinfection may alleviate WT vaccination‐induced immune imprinting and generate broad neutralization responses 41 .…”

Neutralization of SARS-CoV-2 BA.2.86 and JN.1 by CF501 adjuvant-enhanced immune responses targeting the conserved epitopes in ancestral RBD

“… 26 However, a recent study showed that repeated prototype-based booster vaccines did not improve neutralizing antibodies against Omicron subvariants. 27 In contrast, our study provided solid evidence that the RBD from WT SARS-CoV-2 does contain some conserved epitopes recognized by antibodies such as SA55 and BN03, despite the acceleration of mutations in JN.1, BA.2.86, and XBB subvariants. Even with immune pressure, BA.2.86/JN.1 with over 30 mutations still did not change the conserved epitopes for the bnAbs such as SA55 and BN03, implying that the evolution of SARS-CoV-2 might not break through the completely conserved and unmutated epitopes, thus providing proof of concept for the strategy of “non-changeable against changeable” to develop universal COVID-19 vaccines.…”

A review of the clinical characteristics and management of immunosuppressed patients living with HIV or solid organ transplants infected with SARS-CoV-2 omicron variants

“…Research on omicron shows that, in addition to producing antibodies against vaccine strains, immunization with inactivated vaccines also produced neutralizing antibodies against D614G and delta mutant strains in most HIV-infected individuals, but the neutralizing antibody levels were significantly lower than those in the general population ( 43 ). Wang et al ( 44 ) studied the humoral responses of individuals of different ages receiving different vaccination strategies infected with omicron BA.5/BF.7 before and after breakthrough infection in China from December 2022 to January 2023. They found that the newer variants showed increased immune evasion, and the effectiveness of prototype-based booster vaccine schemes on emerging variants such as CH.1.1 and XBB.1.5 continued to weaken.…”

“…They found that the newer variants showed increased immune evasion, and the effectiveness of prototype-based booster vaccine schemes on emerging variants such as CH.1.1 and XBB.1.5 continued to weaken. Repeated prototype-based booster vaccines may therefore not further enhance neutralizing antibodies against new mutations ( 44 ). Low levels of neutralizing antibodies are an important reason for SARS CoV-2 breakthrough infection ( 45 ), suggesting that antibody responses must be monitored in PLWH after COVID-19 vaccination.…”