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

Abstract

SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in its Spike protein to date. Thus, they may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals in particular in those who have only received a primary immunization scheme. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron sub-lineages BA.1, BA.2, BA.2.12.1, BA.3, BA.4/5, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (96–100%) towards the SARS-CoV-2 B.1 isolate, and minor to moderate reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant and its sub-lineages had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron BA.1 and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination, vector-based AZD1222 and Ad26.CoV2.S performed less well with peak responder rates of 48%, 56% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argue for booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based primary immunization scheme.

Single shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad and durable systemic and mucosal immune responses

“…We next assessed the neutralizing activity of Clec9A-RBD immune sera against a panel of 20 sarbecoviruses, which includes SARS-CoV-2 variants of concern (VOCs), SARS-CoV, and animal CoV from the bat and pangolin lineages [25]. The neutralizing activity against most SARS-CoV-2 VOCs increased over time and persisted throughout the 21-month monitoring period (Figure 2A and S2A), except for Omicron lineages, which was not surprising given the extended repertoire of immune escape mutations and in line with previous reports [26]. Interestingly, neutralizing activity against clade-1B sarbecoviruses from bat and pangolin species (RaTG13, BANAL-52, BANAL-236, GD-1, Gx-P5L) was readily detected at all the time points tested, that increased progressively throughout the 21-month monitoring period (Figures 2A and S2A).…”

Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization

“…Multiple studies have clearly shown that there is significant reduction in neutralization by vaccine-induced antibodies against the Omicron variant of concern, compared to the ancestral SARS-CoV-2 strain as well as prior variants of concern (i.e., Alpha, Delta). [14] , [15] , [16] , [17] Differences in neutralization among Omicron BA subvariants, however, are minimal. A recent review of 178 studies that summarized post-vaccination neutralization against multiple Omicron subvariants showed that in general BA.2 subvariants had similar neutralization capacity after primary series and booster dose vaccination compared to BA.1, for all vaccines tested (i.e., mRNA, vector-based, inactivated, protein subunit); the relative fold reduction in neutralization of BA.2 compared to BA.1 was 0.9 [Inter-quartile range (IQR) 0.7-1.2].…”

Extraordinary Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1 and CA.3.1 Variants

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, continues to circulate across the globe while rapidly evolving. The beginning of 2022 was marked by the emergence of Omicron BA.1/BA1.1 variant, establishing a turning point in the pandemic with decreased pathogenicity [1][2][3][4][5] , increased transmissibility 2 , and enhanced immune escape [6][7][8][9][10][11][12][13] .…”