Dizon, J. P. | Search bioRxiv

bioRxiv2021

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3-6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

immunology↗

bioRxiv2018

Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

A clinical trial was performed to evaluate 3BNC117, a potent anti_HIV_1 antibody, in infected individuals during suppressive antiretroviral therapy (ART) and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative outgrowth assay (Q2VOA) at entry and after 6 months, prior to ATI. Although there were no significant quantitative changes in the size of the reservoir, the composition of circulating reservoir clones varied over the 6_month period before treatment interruption in a manner that did not correlate with antibody sensitivity. The neutralization profile obtained from the reservoir by Q2VOA was predictive of time to rebound after ATI, and thus of antibody efficacy. Although 3BNC117 binding site amino acid variants found in rebound viruses pre_existed in the latent reservoir, only 3 of 217 rebound viruses were identical to 868 latent viruses. Instead many of the rebound viruses appeared to be recombinants, even in individuals with resistant reservoir viruses. By incorporating the possibility of recombination, 63% of the rebound viruses could have derived from the observed latent reservoir. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating reservoir, but instead appear to represent recombinants.\n\nSummaryIn the setting of a clinical trial evaluating the anti_HIV_1 antibody 3BNC117, Cohen et al. demonstrate that rebound viruses that emerge following interruption of antiretroviral therapy are distinct from circulating latent viruses. However, rebound viruses often appear to be recombinants between isolated latent viruses.

clinical trials↗