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Omicron-based vaccine candidate generated to evaluate whether or not immunogenicity might be additional improved

In a current examine posted to the bioRxiv* preprint server, researchers used the human adenovirus sort 26 vector (Ad26)-based vaccine platform to generate a novel vaccine candidate Ad26.COV2.S.529. They evaluated the novel vaccine’s immunogenicity in opposition to the brand new extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) Omicron (BA.1).

Examine: Immunogenicity of an Ad26-based SARS-CoV-2 Omicron Vaccine in Naïve Mice and SARS-CoV-2 Spike Pre-immune Hamsters. Picture Credit score: Viacheslav Lopatin/Shutterstock

Omicron has an unprecedented variety of mutations in its spike (S) protein that weakens the impact of neutralizing antibodies elicited by pure SARS-CoV-2 an infection or vaccination. Latest research confirmed {that a} booster dose with present vaccines, particularly a messenger ribonucleic acid (mRNA) vaccine booster (utilizing Wuhan-Hu-1 S as antigen), conferred lesser safety in opposition to Omicron infections, and the induced immunity additionally waned shortly.

Concerning the examine

Within the present examine, researchers developed a vaccine candidate termed Ad26.COV2.S.529, encoding a stabilized Omicron-based S protein resembling ancestral SARS-CoV-2 Wuhan-Hu-1 S protein. They evaluated immunogenicity in naïve mice and pre-immunized hamsters.

To characterize the S expression of Ad26.COV2.S.529 vaccine in vitro, the staff transduced A549 cells with CV3-25 and angiotensin-converting enzyme 2 (ACE2)-Fragment, crystallizable (Fc). They confirmed that CV3-25-S binding in transduced A549 cells with Ad26.COV2.S or Ad26.COV2.S.529 was comparable, and ACE2-Fc fusion protein binding to each S proteins was comparable.

Notably, the CV3-25 antibody binds to the identical conserved area between the Wuhan Hu-1 and BA.1 S protein; likewise, ACE2-binding affinity is comparable between these two S proteins.

They restricted the examine analyses to the 2 most prevalent SARS-CoV-2 VOCs worldwide – Delta (B.1.617.2) and Omicron. They immunized naïve mice with 108, 109, 1010 viral particles (vp) of Ad26.COV2.S, Ad26.COV2.S.529 or 1010 vp of Ad26 empty mock management vector.

Equally, they immunized hamsters with 107 vp Ad26NCOV006, which encodes the non-stabilized WuhanHu-1 S protein, and the management group with 107 vp of Ad26.empty mock management vector. Six weeks later, the hamsters acquired vaccination with 1010 vp of Ad26.COV2.S, Ad26.COV2.S.529 or vector.

The sera from the check animals (mice and hamsters) have been collected 4 weeks after immunization. The researchers used pseudovirion neutralization assay (psVNA) to guage SARS-CoV-2 Delta and Omicron S neutralization titers.

Examine findings

Earlier research have proven that Omicron S-based mRNA vaccines elicited comparable neutralizing antibody ranges in opposition to Omicron, in comparison with the unique Wuhan-Hu-1 S-based mRNA vaccine in non-human primates (NHPs) immunized with two doses of an mRNA vaccine.

Within the current examine, the authors made some contrasting observations. They noticed that in naïve mice, Ad26.COV2.S.529 however not Ad26.COV2.S induced strong Omicron S neutralizing titers. As well as, Ad26.COV2.S.529 elicited elevated Omicron S neutralizing titers in pre-immune hamsters whereas Ad26.COV2.S didn’t.

The authors have additionally beforehand demonstrated that in pre-immune NHPs, a heterologous booster vaccination with an Ad26 vector-based vaccine (Ad26.COV2.S.351) expressing a stabilized Beta-based S protein in additional than seven months after Ad26.COV2.S vaccination elicited 2.9-fold increased Beta psVNA titers than homologous vaccination with the Ad26.COV2.S.

Nonetheless, there isn’t a information proof for these findings. Therefore, it’s unknown whether or not these variations are associated to the magnitude of immune responses elicited by earlier immunizations, the dosage of vaccinations with the Wuhan-Hu-1 S-based vaccine administered (earlier than receiving the Omicron S-based vaccine), the vaccine platform, or the NHP used for the examine.

A examine carried out in South Africa in the course of the Omicron-induced pandemic wave has proven immunization with a homologous booster dose of Ad26.COV2.S six to 9 months after main vaccination offered greater than 80% safety in opposition to hospitalization in Omicron instances. These examine findings revealed that though vaccine-induced safety conferred low Omicron neutralizing antibody titers, it sustained for an extended period because the vaccine-elicited mobile immunity and generated non-neutralizing antibodies with Fc-functions throughout SARS-CoV-2 variants.

Subsequently, put up 4 weeks of immunization with Ad26.COV2.S, Omicron-neutralizing antibodies weren’t detected in both naïve mice or hamsters. In vitro research confirmed that the expression of S is comparable after transduction with each Ad26.COV2.S and Ad26.COV2.S.529. This discovering instructed that boosting pre-existing neutralizing epitope-specific reminiscence B cells (though low in quantity) or de novo induction of B cells might successfully generate antibodies to neutralize Omicron.

Whereas Ad26.COV2.S.529 vaccination resulted in comparable Delta S neutralization titers as Ad26.COV2.S in pre-immune hamsters, the Delta neutralizing titers have been extraordinarily low in Ad26.COV2.S.529 vaccinated naïve mice. Collectively, these findings indicated that in comparison with homologous S protein immunization, heterologous immunization with Ad26.COV2.S.529 induced broadly neutralizing antibody response in animals with pre-existing immunity to Wuhan Hu-1 S.


Total, the vaccine candidate developed within the present examine elicited strong Omicron S neutralizing titers in pre-immune hamsters and naïve mice. This discovering is in settlement with earlier research carried out on  Omicron-based RNA vaccines in naïve NHPs.

*Necessary discover

bioRxiv publishes preliminary scientific stories that aren’t peer-reviewed and, due to this fact, shouldn’t be considered conclusive, information medical observe/health-related conduct, or handled as established info.



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