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MRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant.

ABSTRACT: Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 months), distantly (6-12 months), or an additional "booster" dose, while accounting for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinees. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron, only 4-6-fold lower than wild type, suggesting enhanced cross-reactivity of neutralizing antibody responses. In addition, we find that Omicron pseudovirus infects more efficiently than other variants tested. Overall, this study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.

SUBMITTER: Garcia-Beltran WF

PROVIDER: S-EPMC8733787 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant.

Garcia-Beltran Wilfredo F WF St Denis Kerri J KJ Hoelzemer Angelique A Lam Evan C EC Nitido Adam D AD Sheehan Maegan L ML Berrios Cristhian C Ofoman Onosereme O Chang Christina C CC Hauser Blake M BM Feldman Jared J Roederer Alex L AL Gregory David J DJ Poznansky Mark C MC Schmidt Aaron G AG Iafrate A John AJ Naranbhai Vivek V Balazs Alejandro B AB

Cell 20220106 3

Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 ...[more]

PMID: 34995482

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Project description:BackgroundThe omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster.MethodsIn this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR.FindingsBetween Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2-52·4). Estimated effectiveness was 52·5% (51·3-53·7) for an mRNA-1273 booster and 46·2% (43·5-48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5-61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford-AstraZeneca), 55·3% (52·3-58·2) with mRNA-1273 (Moderna), 49·7% (48·3-51·1) with BNT162b2 (Pfizer-BioNTech), and 48·0% (42·5-53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0-47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0-53·3) if administered more than 180 days after primary scheduled completion.InterpretationBooster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster.FundingNone.

Project description:Mucosal immunity plays a pivotal role in providing comprehensive protection against upper-airway infections and effectively limiting the shedding and transmission of SARS-CoV-2. Despite its critical importance, there remains a notable absence of nasal spray vaccines endorsed for global use by the World Health Organization. This could be due to the inability of current intranasal vaccines to induce strong mucosal and systemic responses in humans, thus urgently entailing a next-generation of intranasal COVID-19 vaccines with novel and safe technologies. In this study, we prepared a two-component intranasal vaccine that combines adenovirus vectors with a self-assembled subunit protein. Specifically, the adenovirus vector expresses the spike protein of XBB.1.5 variant (Ad5XBB.1.5), and were mixed with the recombinant protein that developed derived from the receptor binding domain (RBD) of XBB.1.5 (RBDXBB.1.5-HR). Combination of Ad5XBB.1.5 and RBDXBB.1.5-HR elicited superior humoral and cellular immunity against XBB.1.5-included variants compared with the individual components. Importantly, the STING signaling pathway was found to be crucial for the adjuvant effect of the adenovirus vector. In addition, to increase the broad-spectrum neutralizing capacities, a trimeric protein derived from the BA.5 variant (RBDBA.5-HR) was incorporated to formulate a three-component vaccine (Ad5XBB.1.5+RBDXBB.1.5-HR+RBDBA.5-HR), indicating the utilization of a combination of an adenovirus-vectored and subunit protein vaccines has the potential to serve as a next-generation intranasal vaccine platform. Of note, intranasally delivery of two-component vaccine provided protective immunity against live Omicron XBB.1.16 virus challenge in mice. Furthermore, the combination of adenovirus and subunit protein vaccine demonstrates excellent tolerability and safety in human subjects, and is able to induce enhanced mucosal immunity as well as high levels of sera neutralizing antibody in all participants. These findings underscore its suitability for clinical application in the prevention of SARS-CoV-2 variants encompassing XBB lineages.

Dataset Information

MRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant.

Publications

mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant.

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