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biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.12.12.472269


The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals. Most (26 out of 29) receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only three mAbs, including the ACE2-mimicking S2K146 mAb, retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab, S2X259 and S2H97, neutralized Omicron. The magnitude of Omicron-mediated immune evasion and the acquisition of binding to mouse ACE2 mark a major SARS-CoV-2 mutational shift. Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.

biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.12.07.471590


In this work we evaluated recombinant receptor binding domain (RBD) based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus Alum, AddaS03, AddaVax or the combination of Alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and Alum as adjuvants have a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus Alum, AddaVax or AddaS03. Antibodies induced with the formulation containing U-Omp19 not only increased their neutralization capacity against the wild-type virus but also cross neutralized alpha, lambda and gamma variants with similar potency. Also, addition of U-Omp19 to vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+Alum formulation induced RBD-specific Th1 and CD8 + T cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal SARS-CoV-2 challenge of K18-hACE2 mice.

medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.08.22.21262186


Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we observed a similar process after Sputnik V vaccination. We examined the longitudinal antibody responses and viral neutralizing capacity to variants of concern (VOCs: Alpha, Beta, Gamma, and Delta) and a broadly spread variant of interest (VOI: Lambda) in volunteers up to 6 months after receiving the Sputnik V vaccine in Argentina. A collection of 1,800 serum samples obtained between January and August 2021 was used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing potency to the first-wave linages of SARS-CoV-2 and VOC increases within four months of vaccination, suggesting that antibody maturation occurs. This increase was more evident for the Beta and Gamma variants, which showed the highest propensity for neutralization escape. Our observations suggest that protection increases over the six months following vaccination as a consequence of antibody maturation, resulting in improved potency of antibodies to viral escape mutations.

Severe Acute Respiratory Syndrome , COVID-19