Publications by authors named "F W Alt"
Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env).
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- * Our research found that over 90% of CSR junctions in healthy individuals were due to deletional recombination, revealing two main CSR junction patterns: one linked to IgG and IgA with a high prevalence of Sµ-Sγ junctions, and another mainly associated with Sµ-Sα junctions.
- * The study indicates that the effectiveness of classical nonhomologous end joining (c-NHEJ) pathways in B cells is important for CSR regulation, with the two identified signatures suggesting different mechanisms of recombination
Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.
View Article and Find Full Text PDFNucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unlike SARS-CoV-2 neutralizing antibodies that are readily made, HIV-1 bnAb induction is disfavored by the immune system because of the rarity of bnAb B cell precursors and the cross-reactivity of bnAbs targeting certain Env epitopes with host molecules, thus requiring optimized immunogen design.
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