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Gherasim, C.

Publications and source records attributed to Gherasim, C..

4 recordsLinked to original sources

Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC

SARS-CoV-2 continues to evolve and spread around the world, and it remains critical to understand the functional consequences of mutations that lead to dominant viral variants. KP.3.1.1 is currently the most prevalent subvariant worldwide, while the recombinant subvariant XEC is exhibiting the fastest growth rate. Here we measured the in vitro neutralization of KP.3.1.1 and XEC by human sera, monoclonal antibodies, and soluble hACE2 receptor relative to their parental subvariants KP.3 and JN.1. KP.3.1.1 and XEC were slightly more resistant (1.3-1.6-fold) than KP.3 to serum neutralization, and the resultant antigenic map showed that the new subvariants are antigenically similar. Both also demonstrated greater resistance to neutralization by select monoclonal antibodies and soluble hACE2, all of which target the top of the viral spike. Our findings suggested that upward motion of the receptor-binding domain in spike is partially hindered by the N-terminal-domain mutations found KP.3.1.1 and XEC, thereby allowing these subvariants to better evade serum antibodies that target the viral spike when it is in the up position and thus having a growth advantage in the population.

microbiology↗

Robust SARS-CoV-2 Neutralizing Antibodies Sustained through Three Months Post XBB.1.5 mRNA Vaccine Booster

SARS-CoV-2-neutralizing antibodies were substantially expanded one month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remained unknown. Here, we addressed this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from 39 adult participants obtained at [~]1 month and [~]3 months post an XBB.1.5 MV booster. Our findings indicate that the resultant neutralizing antibody titers were robust and generally maintained at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster.

immunology↗

XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants

COVID-19 vaccines have recently been updated with the spike protein of SARS-CoV-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine (XBB.1.5 MV) to uninfected individuals boosted serum virus-neutralization antibodies significantly against not only XBB.1.5 (27.0-fold) and the currently dominant EG.5.1 (27.6-fold) but also key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold). In individuals previously infected by an Omicron subvariant, serum neutralizing titers were boosted to highest levels (1,504-to-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines to further protect the public.

immunology↗

Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot

The SARS-CoV-2 Omicron variant and its numerous sub-lineages have exhibited a striking ability to evade humoral immune responses induced by prior vaccination or infection. The Food and Drug Administration (FDA) has recently granted Emergency Use Authorizations (EUAs) to new bivalent formulations of the original Moderna and Pfizer mRNA SARS-CoV-2 vaccines that target both the ancestral strain as well as the Omicron BA.4/BA.5 variant. Despite their widespread use as a vaccine boost, little is known about the antibody responses induced in humans. Here, we collected sera from several clinical cohorts: individuals after three or four doses of the original monovalent mRNA vaccines, individuals receiving the new bivalent vaccines as a fourth dose, and individuals with BA.4/BA.5 breakthrough infection following mRNA vaccination. Using pseudovirus neutralization assays, these sera were tested for neutralization against an ancestral SARS-CoV-2 strain, several Omicron sub-lineages, and several related sarbecoviruses. At ~3-5 weeks post booster shot, individuals who received a fourth vaccine dose with a bivalent mRNA vaccine targeting BA.4/BA.5 had similar neutralizing antibody titers as those receiving a fourth monovalent mRNA vaccine against all SARS-CoV-2 variants tested, including BA.4/BA.5. Those who received a fourth monovalent vaccine dose had a slightly higher neutralizing antibody titers than those who received the bivalent vaccine against three related sarbecoviruses: SARS-CoV, GD-Pangolin, and WIV1. When given as a fourth dose, a bivalent mRNA vaccine targeting Omicron BA.4/BA.5 and an ancestral SARS-CoV-2 strain did not induce superior neutralizing antibody responses in humans, at the time period tested, compared to the original monovalent vaccine formulation.

microbiology↗