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Message: <blockquote data-quote="imhotep" data-source="post: 29935692" data-attributes="member: 562115">HIV virus mutates fast, really very fast. Although a person initially becomes infected with one or a few HIV strains, the virus replicates and mutates quickly, resulting in a "swarm" of viral strains existing in a single body. This is why it's hard to develop a vaccine for HIV.But scientists at Scripps Research; IAVI; the Ragon Institute of Mass General, MIT, and Harvard; La Jolla Institute for Immunology; and additional institutions have conducted a series of preclinical trials indicating that they're potentially closer to an immunization regimen than ever before - one that could produce rare antibodies that would be effective against a wide range of HIV strains.This HIV vaccine strategy involves stimulating the body to produce mature broadly neutralizing antibodies (bnAbs). bnAbs are among the immune system's key players in fighting HIV, since they can block many variants of the virus. The problem is that bnAbs produced by the human body are rare. The IAVI trial, spearheaded in part by Schief, focused on inducing the immune cells that could eventually evolve into the right bnAbs-;ones that could protect host cells from multiple HIV strains. These precursor immune cells, known as B cells, were stimulated with the help of a priming immunogen-;a customized molecule to "prime" the immune system and elicit responses from the correct precursor cells.But the primer also requires additional "booster" immunogens to coax the immune system into producing not just precursor cells, but coveted VRC01-class bnAbs - a rare and specific class of antibodies known to neutralize more than 90 percent of diverse HIV strains. Boosters are also needed for the production of BG18 - another important bnAb class that binds to sugars on the HIV spike protein. That's where the new studies come in:  Researchers developed immunization regimens that could prime either VRC01 or BG18 precursors, and subsequently boost those precursors further down the path toward becoming bnAbs.SUMMARYGermline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4-binding site of the HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle–encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as a soluble self-assembling nanoparticle in mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation without exclusionary competition. Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.</blockquote>

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