Absence of neutralizing antibodies against the Omicron SARS-CoV-2 variant in convalescent sera from individuals infected with the ancestral SARS-CoV-2 virus or its Gamma variant.

The aim of the present study was to evaluate if neutralizing antibody responses induced by infection with the SARS-CoV-2 strain that was dominant at the beginning of the pandemic or by the Gamma variant was effective against the Omicron variant. Convalescent sera from 109 individuals, never exposed to a SARS-CoV-2 vaccine, who had mild or moderate symptoms not requiring hospitalization following either a documented SARS-CoV-2 ancestral strain infection or a Gamma variant infection, were assayed for in vitro neutralizing antibody activity against their original strains and the Omicron variant. Following an infection with the ancestral strain, 56 (93.3%), 45 (77.6%) and 1 (1.7%) serum sample were positive for neutralizing antibodies against the ancestral, Gamma variant, and Omicron variant, respectively. After infection with the Gamma variant, 43 (87.8%) and 2 (4.1%) sera were positive for neutralizing antibodies against the Gamma and Omicron variants, respectively. Neutralizing antibodies generated following mild or moderate infection with the SARS-CoV-2 ancestral strain or the Gamma variant are not protective against the Omicron variant.

Villas-Boas LS ，Paula AV ，Silva ARD Jr ，Paiao HGO ，Tozetto-Mendoza TR ，Manuli ER ，Leal FE ，Ferraz ABC ，Sabino EC ，Bierrenbach AL ，Witkin SS ，Mendes-Correa MC ... -  《-》

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone.

da Silva ES ，Kohnen M ，Gilson G ，Staub T ，Arendt V ，Hilger C ，Servais JY ，Charpentier E ，Domingues O ，Snoeck CJ ，Ollert M ，Seguin-Devaux C ，Perez-Bercoff D ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, Beta, Delta, and Omicron variants.

SARS-CoV-2 Omicron variant of concern (VOC) has evolved multiple mutations within the spike protein, raising concerns of increased antibody evasion. In this study, we assessed the neutralization potential of COVID-19 convalescent sera and sera from vaccinated individuals against ancestral SARS-CoV-2 and VOCs. The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2 and Beta, Delta, and Omicron VOCs was assessed using a micro-neutralization assay. Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against Beta and Omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the Omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the Delta variant, was not sufficient to induce high neutralizing antibody titers against Omicron. In summary, we demonstrate that convalescent and vaccinated sera display varying levels of SARS-CoV-2 VOC neutralization. Data from this study will inform booster vaccination strategies against SARS-CoV-2 VOCs. This research was funded by the Canadian Institutes of Health Research (CIHR). VIDO receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and from the Canada Foundation for Innovation through the Major Science Initiatives for its CL3 facility.

Banerjee A ，Lew J ，Kroeker A ，Baid K ，Aftanas P ，Nirmalarajah K ，Maguire F ，Kozak R ，McDonald R ，Lang A ，Gerdts V ，Straus SE ，Gilbert L ，Li AX ，Mozafarihashjin M ，Walmsley S ，Gingras AC ，Wrana JL ，Mazzulli T ，Colwill K ，McGeer AJ ，Mubareka S ，Falzarano D ... -  《Med-US》

Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization.

The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralizing antibodies (nAbs) to SARS-CoV-2. To investigate the effects of antigenic variation on neutralization potency of CP, we compared nAb titers against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunization. Samples were assayed from previously SARS-CoV-2 infected donors before (n = 17) and after one (n = 43) or two (n = 71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titers against Wuhan/wild type (WT), Alpha, Beta, and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titers to Omicron used a focus reduction neutralization test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche). Unvaccinated donors showed a geometric mean titer (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralize Beta, Delta, and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/mL was highly predictive of donations with nAb titers of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specificity). Vaccination of previously infected CP donors induced high levels of broadly neutralizing antibodies against circulating antigenic variants of SARS-CoV-2. High titer donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale preselection of high-titer convalescent plasma.

Harvala H ，Nguyen D ，Simmonds P ，Lamikanra AA ，Tsang HP ，Otter A ，Maes P ，Webster M ，Clarkson A ，Kaloyirou F ，Hopkins V ，Laidlaw SM ，Carroll M ，Mora A ，Griffiths A ，MacLennan S ，Estcourt L ，Roberts DJ ... -  《-》

Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCoV boosters and BA.2 infection.

Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.

Wang F ，Huang B ，Deng Y ，Zhang S ，Liu X ，Wang L ，Liu Q ，Zhao L ，Tang L ，Wang W ，Wang X ，Ye F ，Hu W ，Yang H ，Wang S ，Ren J ，Liu X ，Wang C ，Guan X ，Wang R ，Zheng Y ，Zhang X ，Zheng H ，Wu D ，An Z ，Xu W ，Rodewald LE ，Gao GF ，Yin Z ，Tan W ... -  《BMC Medicine》