The worldwide diversity of HIV-1 presents an unprecedented challenge for vaccine development. Antigens derived from natural HIV-1 sequences have elicited only a limited breadth of cellular immune responses in nonhuman primate studies and clinical trials to date. Polyvalent 'mosaic' antigens, in contrast, are designed to optimize cellular immunologic coverage of global HIV-1 sequence diversity. Here we show that mosaic HIV-1 Gag, Pol and Env antigens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors markedly augmented both the breadth and depth without compromising the magnitude of antigen-specific T lymphocyte responses as compared with consensus or natural sequence HIV-1 antigens in rhesus monkeys. Polyvalent mosaic antigens therefore represent a promising strategy to expand cellular immunologic vaccine coverage for genetically diverse pathogens such as HIV-1.
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http://dx.doi.org/10.1038/nm.2089 | DOI Listing |
EBioMedicine
January 2025
Imperial College London, Department of Infectious Disease, UK. Electronic address:
Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.
Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.
Lancet Microbe
November 2024
The Jenner Institute, Nuffield Department of Medicine, Oxford University, Oxford, UK; Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan. Electronic address:
Background: An HIV-1 vaccine is long overdue. Although vaccine research focuses on the induction of broadly neutralising antibodies, challenging infections such as HIV-1 could require parallel induction of protective T cells. It is important to recognise that not all T cells contribute to protection equally.
View Article and Find Full Text PDFIntroduction: Metagenomic research has allowed the identification of numerous viruses present in the human body. Viruses may significantly increase the likelihood of developing intrauterine fetal growth restriction (FGR). The goal of this study was to examine and compare the virome of normal and FGR placentas using proteomic techniques.
View Article and Find Full Text PDFPLoS Pathog
October 2024
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection prevention, Amsterdam, The Netherlands.
An effective human immunodeficiency virus 1 (HIV-1) vaccine will most likely have to elicit broadly neutralizing antibodies (bNAbs) to overcome the sequence diversity of the envelope glycoprotein (Env). So far, stabilized versions of Env, such as SOSIP trimers, have been able to induce neutralizing antibody (NAb) responses, but those responses are mainly strain-specific. Here we attempted to broaden NAb responses by using a multivalent vaccine and applying a number of design improvements.
View Article and Find Full Text PDFNPJ Vaccines
September 2024
Janssen Vaccines & Prevention, Leiden, The Netherlands.
The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates. Moreover, we found high V2 loop sequence identity between the Mos1 vaccine component and the SHIV challenge strain, while the vaccine showed considerably lower V2 identity to globally circulating HIV-1 sequences.
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