Antigenic characterization of SARS-CoV-2 Omicron subvariants XBB.1.5,BQ.1,BQ.1.1,BF.7 and BA.2.75.2

Dear Editor,Recently,a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities,in particular BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5.1 Unsurprisingly,these new subvariants are quickly gaining prevalence worldwide.In fact,some of them have outcompeted BA.5 in the USA according to CDC’s national genomic surveillance data in which,as of 6th February 2023,XBB.1.5,BQ.1.1,BQ.1,XBB and BF.7 have achieved a dominance of 66.4%,19.9%,7.3%,2.3%and 0.5%in the USA,as compared to 0.5%for BA.5.In this report,using plasma samples collected from individuals following different vaccination strategies and COVID-19 convalescent donors,we performed pseudoviral neutralization assays to confirm severe reductions in neutralization titers against BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5 in comparison to other Omicron sub-lineages.XBB and XBB.1.5 were shown to be remarkably resistant to plasma neutralization in all tested cohorts.By comparing the differential neutralization profiles,we found that a heterologous booster with an aerosolized vaccine following 2 doses of inactivated vaccine seemed to be superior to other vaccination strategies.

Assessment of infectivity and the impact on neutralizing activity of immune sera of the COVID-19 variant,CAL.20C

Dear Editor,New variants of SARS-CoV-2 have been emerging since the initial outbreak in 2019;1 one of the latest ones was identified in Southern California in October 2020 and was subsequently detected in 26 other states in the United States as well as other countries as of January 2021.

The SARS-CoV-2 spike L452R-E484Q variant in the Indian B.1.617 strain showed significant reduction in the neutralization activity of immune sera

To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1(dominant variant identified in the current India outbreak)on the infectivity and neutralization activities of the immune sera,L452R and E484Q(L452R-E484Q variant),pseudotyped virus was constructed(with the D614G background).The impact on binding with the neutralizing antibodies was also assessed with an ELISA assay.Pseudotyped virus carrying a L452R-E484Q variant showed a comparable infectivity compared with D614G.However,there was a significant reduction in the neutralization activity of the immune sera from non-human primates vaccinated with a recombinant receptor binding domain(RBD)protein,convalescent patients,and healthy vaccinees vaccinated with anmRNA vaccine.In addition,there was a reduction in binding of L452R-E484Q-D614G protein to the antibodies of theimmune sera fromvaccinated nonhuman primates.These results highlight the interplay between infectivity and other biologic factors involved in the natural evolution of SARS-CoV-2.Reduced neutralization activities against the L452R-E484Q variant will have an impact on health authority planning and implications for the vaccination strategy/newvaccine development.

Heterologous mRNA vaccine booster increases neutralization of SARS-CoV-2 Omicron BA.2 variant

Dear Editor,Emerging epidemiology data indicate that the Omicron BA.2 sublineage is expected to become the dominant strain owing to its enhanced transmissibility.1 The BA.1 sublineage reduced the efficacy of neutralizing antibodies.2,3 The BA.2 sublineage may possess similar neutralizing antibody evasion.3 However,booster(3rd dose)vaccination strategies,or three exposures to the SARS-CoV2 spike protein through natural infection elicits strong neutralizing antibody responses.This raises the question of whether booster doses also elicit neutralizing antibody responses against BA.2.We present in this study the neutralization activity of serum from human recipients of homologous booster(three doses of CoronaVac inactivated vaccine)or heterologous booster(inactivated vaccine priming dose with BnT162b2 third dose)vaccine regimens against pseudovirus containing the Omicron BA.2 spike protein.We also evaluated the neutralizing activities of 6 monoclonal antibodies,and serum from monkeys vaccinated with a recombinant RBD protein vaccine.Finally,we also evaluated cell entry mediated by the Omicron BA.2 spike protein.