Carbonetti Sara, Oliver Brian G, Glenn Jolene, Stamatatos Leonidas, Sather D Noah
Seattle BioMed, Seattle, Washington, United States of America.
Seattle BioMed, Seattle, Washington, United States of America ; Department of Global Health, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2014 Jan 23;9(1):e86905. doi: 10.1371/journal.pone.0086905. eCollection 2014.
We evaluated four gp140 Envelope protein vaccine immunogens that were derived from an elite neutralizer, subject VC10042, whose plasma was able to potently neutralize a wide array of genetically distinct HIV-1 isolates. We sought to determine whether soluble Envelope proteins derived from the viruses circulating in VC10042 could be used as immunogens to elicit similar neutralizing antibody responses by vaccination. Each gp140 was tested in its trimeric and monomeric forms, and we evaluated two gp140 trimer vaccine regimens in which adjuvant was supplied at all four immunizations or at only the first two immunizations. Interestingly, all four Envelope immunogens elicited high titers of cross-reactive antibodies that recognize the variable regions V1V2 and are potentially similar to antibodies linked with a reduced risk of HIV-1 acquisition in the RV144 vaccine trial. Two of the four immunogens elicited neutralizing antibody responses that neutralized a wide array of HIV-1 isolates from across genetic clades, but those responses were of very low potency. There were no significant differences in the responses elicited by trimers or monomers, nor was there a significant difference between the two adjuvant regimens. Our study identified two promising Envelope immunogens that elicited anti-V1V2 antibodies and broad, but low potency, neutralizing antibody responses.
我们评估了四种源自精英中和者VC10042的gp140包膜蛋白疫苗免疫原,其血浆能够有效中和多种基因不同的HIV-1分离株。我们试图确定源自VC10042体内循环病毒的可溶性包膜蛋白是否可用作免疫原,通过疫苗接种引发类似的中和抗体反应。对每种gp140的三聚体和单体形式进行了测试,并且我们评估了两种gp140三聚体疫苗接种方案,其中在所有四次免疫接种时或仅在前两次免疫接种时提供佐剂。有趣的是,所有四种包膜免疫原均引发了高滴度的交叉反应性抗体,这些抗体识别可变区V1V2,并且可能类似于RV144疫苗试验中与降低HIV-1感染风险相关的抗体。四种免疫原中的两种引发了中和抗体反应,可中和来自不同基因分支的多种HIV-1分离株,但这些反应的效力非常低。三聚体或单体引发的反应之间没有显著差异,两种佐剂方案之间也没有显著差异。我们的研究确定了两种有前景的包膜免疫原,它们引发了抗V1V2抗体以及广泛但效力较低的中和抗体反应。