Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates

Abstract The development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A criti...

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Autores principales:	Kevin O. Saunders, Norbert Pardi, Robert Parks, Sampa Santra, Zekun Mu, Laura Sutherland, Richard Scearce, Maggie Barr, Amanda Eaton, Giovanna Hernandez, Derrick Goodman, Michael J. Hogan, Istvan Tombacz, David N. Gordon, R. Wes Rountree, Yunfei Wang, Mark G. Lewis, Theodore C. Pierson, Chris Barbosa, Ying Tam, Xiaoying Shen, Guido Ferrari, Georgia D. Tomaras, David C. Montefiori, Drew Weissman, Barton F. Haynes
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/19cac807096e43e39da4251a08ade56b
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spelling	oai:doaj.org-article:19cac807096e43e39da4251a08ade56b2021-12-02T14:17:30ZLipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates10.1038/s41541-021-00307-62059-0105https://doaj.org/article/19cac807096e43e39da4251a08ade56b2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00307-6https://doaj.org/toc/2059-0105Abstract The development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. Here, we show that mRNA-LNP immunization compared to protein immunization elicits either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope or HIV-1 Env gp160 induces durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 μg are immunogenic in macaques. Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Such vaccines would be as or more immunogenic than adjuvanted recombinant protein vaccines in primates.Kevin O. SaundersNorbert PardiRobert ParksSampa SantraZekun MuLaura SutherlandRichard ScearceMaggie BarrAmanda EatonGiovanna HernandezDerrick GoodmanMichael J. HoganIstvan TombaczDavid N. GordonR. Wes RountreeYunfei WangMark G. LewisTheodore C. PiersonChris BarbosaYing TamXiaoying ShenGuido FerrariGeorgia D. TomarasDavid C. MontefioriDrew WeissmanBarton F. HaynesNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Kevin O. Saunders Norbert Pardi Robert Parks Sampa Santra Zekun Mu Laura Sutherland Richard Scearce Maggie Barr Amanda Eaton Giovanna Hernandez Derrick Goodman Michael J. Hogan Istvan Tombacz David N. Gordon R. Wes Rountree Yunfei Wang Mark G. Lewis Theodore C. Pierson Chris Barbosa Ying Tam Xiaoying Shen Guido Ferrari Georgia D. Tomaras David C. Montefiori Drew Weissman Barton F. Haynes Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates
description	Abstract The development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. Here, we show that mRNA-LNP immunization compared to protein immunization elicits either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope or HIV-1 Env gp160 induces durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 μg are immunogenic in macaques. Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Such vaccines would be as or more immunogenic than adjuvanted recombinant protein vaccines in primates.
format	article
author	Kevin O. Saunders Norbert Pardi Robert Parks Sampa Santra Zekun Mu Laura Sutherland Richard Scearce Maggie Barr Amanda Eaton Giovanna Hernandez Derrick Goodman Michael J. Hogan Istvan Tombacz David N. Gordon R. Wes Rountree Yunfei Wang Mark G. Lewis Theodore C. Pierson Chris Barbosa Ying Tam Xiaoying Shen Guido Ferrari Georgia D. Tomaras David C. Montefiori Drew Weissman Barton F. Haynes
author_facet	Kevin O. Saunders Norbert Pardi Robert Parks Sampa Santra Zekun Mu Laura Sutherland Richard Scearce Maggie Barr Amanda Eaton Giovanna Hernandez Derrick Goodman Michael J. Hogan Istvan Tombacz David N. Gordon R. Wes Rountree Yunfei Wang Mark G. Lewis Theodore C. Pierson Chris Barbosa Ying Tam Xiaoying Shen Guido Ferrari Georgia D. Tomaras David C. Montefiori Drew Weissman Barton F. Haynes
author_sort	Kevin O. Saunders
title	Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates
title_short	Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates
title_full	Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates
title_fullStr	Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates
title_full_unstemmed	Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates
title_sort	lipid nanoparticle encapsulated nucleoside-modified mrna vaccines elicit polyfunctional hiv-1 antibodies comparable to proteins in nonhuman primates
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/19cac807096e43e39da4251a08ade56b
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Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates

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