Optimal sequence-based design for multi-antigen HIV-1 vaccines using minimally distant antigens
The immense global diversity of HIV-1 is a significant obstacle to developing a safe and effective vaccine. We recently showed that infections established with multiple founder variants are associated with the development of neutralization breadth years later. We propose a novel vaccine design strat...
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| Veröffentlicht in: | PLoS computational biology 2022-10, Vol.18 (10), p.e1010624-e1010624 |
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| creator | Lewitus, Eric Hoang, Jennifer Li, Yifan Bai, Hongjun Rolland, Morgane |
| description | The immense global diversity of HIV-1 is a significant obstacle to developing a safe and effective vaccine. We recently showed that infections established with multiple founder variants are associated with the development of neutralization breadth years later. We propose a novel vaccine design strategy that integrates the variability observed in acute HIV-1 infections with multiple founder variants. We developed a probabilistic model to simulate this variability, yielding a set of sequences that present the minimal diversity seen in an infection with multiple founders. We applied this model to a subtype C consensus sequence for the Envelope (Env) (used as input) and showed that the simulated Env sequences mimic the mutational landscape of an infection with multiple founder variants, including diversity at antibody epitopes. The derived set of multi-founder-variant-like, minimally distant antigens is designed to be used as a vaccine cocktail specific to a HIV-1 subtype or circulating recombinant form and is expected to promote the development of broadly neutralizing antibodies. |
| doi_str_mv | 10.1371/journal.pcbi.1010624 |
| format | Article |
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We recently showed that infections established with multiple founder variants are associated with the development of neutralization breadth years later. We propose a novel vaccine design strategy that integrates the variability observed in acute HIV-1 infections with multiple founder variants. We developed a probabilistic model to simulate this variability, yielding a set of sequences that present the minimal diversity seen in an infection with multiple founders. We applied this model to a subtype C consensus sequence for the Envelope (Env) (used as input) and showed that the simulated Env sequences mimic the mutational landscape of an infection with multiple founder variants, including diversity at antibody epitopes. The derived set of multi-founder-variant-like, minimally distant antigens is designed to be used as a vaccine cocktail specific to a HIV-1 subtype or circulating recombinant form and is expected to promote the development of broadly neutralizing antibodies.</description><identifier>ISSN: 1553-7358</identifier><identifier>ISSN: 1553-734X</identifier><identifier>EISSN: 1553-7358</identifier><identifier>DOI: 10.1371/journal.pcbi.1010624</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>AIDS vaccines ; Amino acids ; Analysis ; Antibodies ; Antigenic determinants ; Antigens ; Biology and Life Sciences ; Computer and Information Sciences ; Conserved sequence ; Ecology and Environmental Sciences ; Epitopes ; HIV ; Human immunodeficiency virus ; Infections ; Learning models (Stochastic processes) ; Medicine and Health Sciences ; Methods ; Neutralization ; Probabilistic models ; Probability ; Product development ; Research and Analysis Methods ; Vaccines ; Viruses</subject><ispartof>PLoS computational biology, 2022-10, Vol.18 (10), p.e1010624-e1010624</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Lewitus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Lewitus et al 2022 Lewitus et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c568t-d0bcbae5134cec10d234a72faffdbea9f528e300866ab06929e2d57fcc914ddc3</citedby><cites>FETCH-LOGICAL-c568t-d0bcbae5134cec10d234a72faffdbea9f528e300866ab06929e2d57fcc914ddc3</cites><orcidid>0000-0002-3501-3974 ; 0000-0001-7038-2671 ; 0000-0003-3650-8490 ; 0000-0001-6459-2437</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621458/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621458/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids></links><search><contributor>De Boer, Rob J.</contributor><creatorcontrib>Lewitus, Eric</creatorcontrib><creatorcontrib>Hoang, Jennifer</creatorcontrib><creatorcontrib>Li, Yifan</creatorcontrib><creatorcontrib>Bai, Hongjun</creatorcontrib><creatorcontrib>Rolland, Morgane</creatorcontrib><title>Optimal sequence-based design for multi-antigen HIV-1 vaccines using minimally distant antigens</title><title>PLoS computational biology</title><description>The immense global diversity of HIV-1 is a significant obstacle to developing a safe and effective vaccine. We recently showed that infections established with multiple founder variants are associated with the development of neutralization breadth years later. We propose a novel vaccine design strategy that integrates the variability observed in acute HIV-1 infections with multiple founder variants. We developed a probabilistic model to simulate this variability, yielding a set of sequences that present the minimal diversity seen in an infection with multiple founders. We applied this model to a subtype C consensus sequence for the Envelope (Env) (used as input) and showed that the simulated Env sequences mimic the mutational landscape of an infection with multiple founder variants, including diversity at antibody epitopes. The derived set of multi-founder-variant-like, minimally distant antigens is designed to be used as a vaccine cocktail specific to a HIV-1 subtype or circulating recombinant form and is expected to promote the development of broadly neutralizing antibodies.</description><subject>AIDS vaccines</subject><subject>Amino acids</subject><subject>Analysis</subject><subject>Antibodies</subject><subject>Antigenic determinants</subject><subject>Antigens</subject><subject>Biology and Life Sciences</subject><subject>Computer and Information Sciences</subject><subject>Conserved sequence</subject><subject>Ecology and Environmental Sciences</subject><subject>Epitopes</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Infections</subject><subject>Learning models (Stochastic processes)</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Neutralization</subject><subject>Probabilistic 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| subjects | AIDS vaccines Amino acids Analysis Antibodies Antigenic determinants Antigens Biology and Life Sciences Computer and Information Sciences Conserved sequence Ecology and Environmental Sciences Epitopes HIV Human immunodeficiency virus Infections Learning models (Stochastic processes) Medicine and Health Sciences Methods Neutralization Probabilistic models Probability Product development Research and Analysis Methods Vaccines Viruses |
| title | Optimal sequence-based design for multi-antigen HIV-1 vaccines using minimally distant antigens |
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