The development of a protective vaccine remains a top priority for the control of the HIV/AIDS pandemic. Here, we show that a messenger RNA (mRNA) vaccine co-expressing membrane-anchored HIV-1 envelope (Env) and simian immunodeficiency virus (SIV) Gag proteins to generate virus-like particles (VLPs) induces antibodies capable of broad neutralization and reduces the risk of infection in rhesus macaques. In mice, immunization with co-formulated env and gag mRNAs was superior to env mRNA alone in inducing neutralizing antibodies. Macaques were primed with a transmitted-founder clade-B env mRNA lacking the N276 glycan, followed by multiple booster immunizations with glycan-repaired autologous and subsequently bivalent heterologous envs (clades A and C). This regimen was highly immunogenic and elicited neutralizing antibodies against the most prevalent (tier-2) HIV-1 strains accompanied by robust anti-Env CD4 + T cell responses. Vaccinated animals had a 79% per-exposure risk reduction upon repeated low-dose mucosal challenges with heterologous tier-2 simian-human immunodeficiency virus (SHIV AD8). Thus, the multiclade env-gag VLP mRNA platform represents a promising approach for the development of an HIV-1 vaccine. Nature MediciNedegrees of protection in non-human primate models [31][32][33][34][35] . Some approaches have used messenger RNA (mRNA) as a vector, resulting in the induction of polyfunctional antibody responses comparable to those induced by protein immunization, as well as efficient T cell responses [36][37][38] . Altogether, the evidence so far accumulated suggests that no individual factor will determine the ultimate success of a bNAb-inducing HIV-1 vaccine, which probably requires a combination of efficient precursor B cell priming, optimization of Env design and presentation, and sustained heterologous Env boosting. ResultsDesign of an env-gag VLP mRNA vaccine platform. Critical advancements in mRNA technology over the past two decades 39,40 have enabled the development of mRNA-based vaccine platforms, which have recently shown remarkable effectiveness against ). Taking advantage of the versatility of mRNA as an expression system, we designed a novel vaccine platform by combining a series of features that we postulated to be critical for the elicitation of protective antibody responses. These include, first, the use of mRNA as a vehicle in order to instruct host cells to endogenously express membrane-bound viral glycoproteins and decorate them with native N-linked glycosylation; second, the use of full-length or minimally truncated HIV-1 Envs that do not expose distractive immunodominant epitopes, unlike truncated soluble trimers; third, co-expression of Env with Gag in order to promote the in vivo production of virus-like particles (VLPs), which closely mimic native viral particles produced by HIV-1 infection; fourth, initial priming with an Env capable of engaging germline bNAb precursors; and last, intensive heterologous boosting with tier-2 Envs from different clades in order to selectively expan...

The 1988 Agricultural Economics and Land Ownership Suryey allows a more thorough analysis of the role of women as farmland owners. Women farmland owners are predominately nonoperators-that is, they rent their land to others. This analysis focuses on whether gender affects landlord participation in the selection of fertilizer and chemicals on leased land. Findings indicate that women landlords are less likely than men to participate in this management decision.

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