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Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial.

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Titel: Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial.
Autoren: Parks, K. Rachael, Moodie, Zoe, Allen, Mary A., Yen, Catherine, Furch, Briana D., MacPhee, Kellie J., Ozorowski, Gabriel, Heptinstall, Jack, Hahn, William O., Zheng, Zihan, Lu, Huiyin, Grant, Shannon, Domin, Elize, Duff, Michael O., Seese, Aaron, Marini-Macouzet, Constanza, Ballweber-Fleming, Lamar, Lee, Wen-Hsin, Cottrell, Christopher A., Liguori, Alessia
Quelle: Science Translational Medicine; 7/30/2025, Vol. 17 Issue 809, p1-14, 14p
Schlagwörter: HIV, VACCINES, SAFETY, IMMUNE response, CLINICAL trials, HIV antibodies, VIRAL envelopes, HUMORAL immunity
Abstract: mRNA technology might accelerate development of an urgently needed preventive human immunodeficiency virus (HIV) vaccine. We evaluated the safety and immunogenicity of three mRNA-encoded envelope trimers, including two doses of soluble and membrane-anchored forms, in a randomized, open-label, phase 1 clinical trial. Vaccines were generally well tolerated, although 6.5% (7 of 108) of participants developed urticaria, a higher proportion than seen with other mRNA vaccines. mRNA-encoded trimers induced strong envelope-specific B and T cell responses. Immunization with membrane-anchored trimers, intended to obscure epitopes at the trimer base targeted by nonneutralizing antibodies, reduced the frequency of base-binding serum antibodies in comparison with soluble trimers. Three immunizations elicited autologous tier 2 serum neutralizing antibodies in 80% of vaccinees receiving the membrane-anchored trimers, in contrast to only 4% receiving the soluble trimer. Thus, with demonstration of more favorable safety, mRNA-encoded membrane-anchored HIV envelope trimers represent a promising platform for HIV vaccine clinical development. Editor's summary: Vaccines for human immunodeficiency virus (HIV) usually target the envelope (Env) trimer that is present on the surface of virions. However, protein-based vaccines require the Env trimer to be soluble; this creates a site at the base of the Env for antibodies to bind that is unable to confer protection against infection. In two papers, Ramezani-Rad et al. and Parks et al. take advantage of mRNA vaccines to circumvent this problem. mRNAs are translated into proteins within the vaccine recipient's cells, enabling the authors to produce membrane-bound versions of the Env trimer. Ramezani-Rad et al. demonstrated that this approach elicited antibodies that bound to the intended, nonbase regions of the Env in preclinical models, supporting progression of this vaccine to clinical trials. Parks et al. report results of a phase 1 clinical trial, showing that vaccination of humans with a membrane-bound Env trimer elicits productive antibody responses, consistent with the preclinical studies. This pair of papers highlights the advantages of mRNA vaccines, especially for HIV vaccine design. —Courtney Malo [ABSTRACT FROM AUTHOR]
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Datenbank: Complementary Index
Beschreibung
Abstract:mRNA technology might accelerate development of an urgently needed preventive human immunodeficiency virus (HIV) vaccine. We evaluated the safety and immunogenicity of three mRNA-encoded envelope trimers, including two doses of soluble and membrane-anchored forms, in a randomized, open-label, phase 1 clinical trial. Vaccines were generally well tolerated, although 6.5% (7 of 108) of participants developed urticaria, a higher proportion than seen with other mRNA vaccines. mRNA-encoded trimers induced strong envelope-specific B and T cell responses. Immunization with membrane-anchored trimers, intended to obscure epitopes at the trimer base targeted by nonneutralizing antibodies, reduced the frequency of base-binding serum antibodies in comparison with soluble trimers. Three immunizations elicited autologous tier 2 serum neutralizing antibodies in 80% of vaccinees receiving the membrane-anchored trimers, in contrast to only 4% receiving the soluble trimer. Thus, with demonstration of more favorable safety, mRNA-encoded membrane-anchored HIV envelope trimers represent a promising platform for HIV vaccine clinical development. Editor's summary: Vaccines for human immunodeficiency virus (HIV) usually target the envelope (Env) trimer that is present on the surface of virions. However, protein-based vaccines require the Env trimer to be soluble; this creates a site at the base of the Env for antibodies to bind that is unable to confer protection against infection. In two papers, Ramezani-Rad et al. and Parks et al. take advantage of mRNA vaccines to circumvent this problem. mRNAs are translated into proteins within the vaccine recipient's cells, enabling the authors to produce membrane-bound versions of the Env trimer. Ramezani-Rad et al. demonstrated that this approach elicited antibodies that bound to the intended, nonbase regions of the Env in preclinical models, supporting progression of this vaccine to clinical trials. Parks et al. report results of a phase 1 clinical trial, showing that vaccination of humans with a membrane-bound Env trimer elicits productive antibody responses, consistent with the preclinical studies. This pair of papers highlights the advantages of mRNA vaccines, especially for HIV vaccine design. —Courtney Malo [ABSTRACT FROM AUTHOR]
ISSN:19466234
DOI:10.1126/scitranslmed.ady6831