The receptor binding domain (RBD) of the SARS-CoV-2 spike protein is the primary target of neutralizing antibodies and is a component of almost all vaccine candidates. Here, RBD immunogens were created with stabilizing amino acid changes that improve the neutralizing antibody response, as well as characteristics for production, storage, and distribution. A computational design and in vitro screening platform identified three improved immunogens, each with approximately nine amino acid changes relative to the native RBD sequence and four key changes conserved between immunogens. The changes are adaptable to all vaccine platforms, are compatible with established changes in SARS-CoV-2 vaccines, and are compatible with mutations in emerging variants of concern. The immunogens elicit higher levels of neutralizing antibodies than native RBD, focus the immune response to structured neutralizing epitopes, and have increased production yields and thermostability. Incorporating these variant-independent amino acid changes in next-generation vaccines may enhance the neutralizing antibody response and lead to pan-SARS-CoV-2 protection.
Malaria elimination requires tools that interrupt parasite transmission. Here, we characterized B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230kDa gamete surface protein Pfs2301–3 to neutralize sexual stage P. falciparum parasites and halt their further spread. We generated nine Pfs230 human monoclonal antibodies (mAbs). One mAb potently blocked transmission to mosquitoes in a complement-dependent manner and reacted strongly to gamete surface while eight mAbs showed only low or no blocking activity. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.
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