Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations

Abstract

Background: SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection. The novel variant of concern Omicron (B.1.1.529) has to date the largest number of amino acid alterations in its Spike protein. Thus, it may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals. Aims: We analysed neutralization activity after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe at peak response and in a longitudinal follow-up with BNT162b2 vaccinees to define immune escape potential of the Omicron VoC. Methods: We tested sera by in vitro neutralization assay towards SARS-CoV-2 B.1, Omicron, Beta and Delta pseudotypes Results: All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (93.3-100%) towards SARS-CoV-2 wild-type, but some reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant had the biggest impact, both in terms of response rates and neutralization titres among responders. Only mRNA-1273 showed a 100% response rate to Omicron and induced the highest titres of neutralizing antibodies, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination or vector-based formulations with AZD1222 or Ad26.CoV2.S performed less well with peak responder rates of 33%, 50% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up and even slightly increased to 47%, indicating cross-protection against Omicron is maintained over time. Conclusions: Overall, our data strongly argues for urgent booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based immunization scheme.

A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease

“…Instead, new vaccines or immunization schedules will likely be evaluated using “immunobridging”: indirectly inferring vaccine efficacy by measuring immunological biomarkers (like neutralizing antibody levels) identified as correlates of protection 53,55,206–208 . Such study designs - not reviewed here - have already been used for early assessment of waning rates 207,209 , identifying potential loses in protection against new variants 24,25,210 , promoting the need for booster doses 24,25,211,212 , justifying heterologous vaccine courses 212,213 , expanding eligible age groups to children 214,215 , and to grant initial emergency approval to some vaccines (e.g. Medigen’s MVC-COV1901 in Taiwan 216 ).…”

“…The emergence of SARS-CoV-2 “variants of concern”, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) further confounds interpretation of estimates obtained from comparably-designed vaccine studies. Some variants are associated with higher viral load 15–19 , evasion of neutralizing antibodies ex vivo 20–25 , and lower vaccine effectiveness 13,19,26–29 . However, separating diminished protection against a variant from the effects of waning immunity, study methodology, or other contextual factors (e.g., lower use of non-pharmaceutical interventions) is complicated by their co-occurrence and endogeneity.…”

“Is Omicron mild”? Testing this narrative with the mutational landscape of its three lineages and response to existing vaccines and therapeutic antibodies

“…Due to the presence of many mutations with known immune evasion potential in Omicron genome, data on neutralization of Omicron, vaccine effectiveness (VE) and immunogenicity comparisons by convalescent and other vaccine sera in homologous prime or homologous/heterologous prime‐boost settings has been released by many research groups from more than 25 different countries. 9 , 20 , 22 , 26 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 A variety of neutralization assays and cell types including in vitro pseudo virus, live virus and real‐life datasets have been used in these studies.…”

“…Early estimates of VE from various countries indicate a significantly reduced effectiveness of the existing vaccines in terms of a decline in neutralizing antibodies produced against Omicron 33 compared to Delta and the ancestral virus in two‐dose vaccinated people, with or without a previous infection. The third booster dose has been shown to raise the antibody levels and help in reversing the declining trends of neutralizing antibodies but only to modest levels 49 , 59 , 65 , 74 , 77 that were observed to be significantly lower when compared to Wuhan‐Hu‐1 virus or even Delta strain.…”

Analysis of anti-Omicron neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

“…The novel VOC Omicron is reducing the efficacy of all vaccines approved to date (unless 3 doses are delivered) [4-19], represents an unexpected boost over CCP usage, with Omicron being treated as an entirely novel virus instead of a SARS-CoV-2 variants. Two years into the pandemics, we are back to the starting line for some therapeutic agents.…”