Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial

Abstract

Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT 05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.

Beta-spike-containing boosters induce robust and functional antibody responses to SARS-CoV-2 in macaques primed with distinct vaccines

“…Our results are consistent with other reports of increased neutralization capacity of monovalent or bivalent Beta-spike-containing boosted NHPs, particularly against Omicron lineages. 40 , 41 We have shown that these boosted humoral responses are not exclusive to neutralizing antibodies. Of particular interest was the highly expanded IgA responses we observed in Beta-spike-containing formulations.…”

Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera

“…Residual titers plotted on the antibody landscape offer a glimpse of how well the landscape can predict titers against a particular variant. In prior antibody landscapes that use antigenic maps with BA.4/BA.5 as the latest variant, the landscapes with plotted residuals show landscapes that accurately fit antibody titers 26,50 . However, in landscapes that include XBB and BQ variants in their antigenic map, the measured titers against BA.4/BA.5 have generally been greater than what the landscape predicts 39 .…”

“…The height of an accurate antibody landscape can be used to infer antibody titers against variants that were not used in making of the landscape 18 . It has been common for antibody landscapes generated with multiple ancestral SARS-CoV-2 vaccinations and infection histories to assume a cone landscape, often with a peak at D614G (ancestral strain) with the landscape gradually tapering as antigenic distance from D614G increases 26,28,39,48,50 . Our study found that booster vaccines or PVIs containing Omicron moderately boosted neutralizing antibodies against Omicron variants more than repeated vaccination with ancestral strain, which has been noted elsewhere 50 .…”

“…Building upon antigenic cartography, antibody landscapes have been useful for characterizing neutralization profiles of individuals who have had multiple antigenic exposures 18,26,28,39,48,50 . The height of an accurate antibody landscape can be used to infer antibody titers against variants that were not used in making of the landscape 18 .…”

“…It has been common for antibody landscapes generated with multiple ancestral SARS-CoV-2 vaccinations and infection histories to assume a cone landscape, often with a peak at D614G (ancestral strain) with the landscape gradually tapering as antigenic distance from D614G increases 26,28,39,48,50 . Our study found that booster vaccines or PVIs containing Omicron moderately boosted neutralizing antibodies against Omicron variants more than repeated vaccination with ancestral strain, which has been noted elsewhere 50 . In addition, we show that booster vaccination with XBB.1.5 increases neutralizing antibodies and thus the landscape even higher than prior bivalent vaccinations or PVIs.…”