Michel nussenzweig nature conservancy

  • We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells.
  • Michel NUSSENZWEIG, Zanvil A. Cohn and Ralph Steinman Professor | Cited by 109982 | of Rockefeller University, New York City (Rockefeller) | Read 688.
  • Peer review information Nature thanks Pamela Bjorkman, Michel Nussenzweig and the other, anonymous, reviewer(s) for their contribution to the.

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    Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost

    Main

    We studied the immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in a longitudinal cohort of 42 volunteers with no prior history of SARS-CoV-2 infection5,6 who were recruited between 21 January 2021 and 14 December 2021 for sequential blood donation. The volunteers received either the Moderna (mRNA-1273; n = 8) or Pfizer-BioNTech (BNT162b2; n = 34) mRNA vaccine. Volunteers ranged in age from 23 to 78 years old; 48% were male and 52% were female (Methods and Supplementary Table 1). Samples were obtained at the following time points: 2.5 weeks after the prime, 1.3 and 5 months after the second vaccine dose and 1 month after the third dose.

    Plasma binding and neutralization

    Plasma IgM, IgG and IgA responses to SARS-CoV-2 Wuhan-Hu-1 receptor-binding domain (RBD) were measured by enzyme-linked immunosorbent assay (ELISA)5,6. While a significant

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    Abstract

    Waves of SARS-CoV-2 infection have resulted from the emergence of viral variants with neutralizing antibody resistance mutations. Simultaneously, repeated antigen exposure has generated affinity matured B cells, producing broadly neutralizing receptor binding domain (RBD)-specific antibodies with activity against emergent variants. To determine how SARS-CoV-2 might escape these antibodies, we subjected chimeric viruses encoding spike proteins from ancestral, BA.1 or BA.2 variants to selection by 40 broadly neutralizing antibodies. We identify numerous examples of epistasis, whereby in vitro selected and naturally occurring substitutions in RBD epitopes that do not confer antibody resistance in the Wuhan-Hu-1 spike, do so in BA.1 or BA.2 spikes. As few as 2 or 3 of these substitutions in the BA.5 spike, confer resistance to nearly all of the 40 broadly neutralizing antibodies, and substantial resistance to plasma from most individuals. Thus, epistasis facilitates the acquis

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    ABSTRACT

    Anti-human immunodeficiency virus type 1 (HIV-1) nonneutralizing antibodies (nnAbs) capable of antibody-dependent cellular cytotoxicity (ADCC) have been identified as a protective immune correlate in the RV144 vaccine efficacy trial. Broadly neutralizing antibodies (bNAbs) also mediate ADCC in cell culture and rely on their Fc region for optimal efficacy in animal models. Here, we selected 9 monoclonal nnAbs and 5 potent bNAbs targeting various epitopes and conformations of the gp120/41 complex and analyzed the potency of the two types of antibodies to bind and eliminate HIV-1-infected cells in culture. Regardless of their neutralizing activity, most of the selected antibodies recognized and killed cells infected with two laboratory-adapted HIV-1 strains. Some nnAbs also bound bystander cells that may have captured viral proteins. However, in contrast to the bNAbs, the nnAbs bound poorly to reactivated infected cells from 8 HIV-positive individuals and did not mediate effe

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