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Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection.

Publication ,  Journal Article
Saunders, KO; Edwards, RJ; Tilahun, K; Manne, K; Lu, X; Cain, DW; Wiehe, K; Williams, WB; Mansouri, K; Hernandez, GE; Sutherland, L; Parks, R ...
Published in: Sci Transl Med
September 7, 2022

A successful HIV-1 vaccine will require induction of a polyclonal neutralizing antibody (nAb) response, yet vaccine-mediated induction of such a response in primates remains a challenge. We found that a stabilized HIV-1 CH505 envelope (Env) trimer formulated with a Toll-like receptor 7/8 agonist induced potent HIV-1 polyclonal nAbs that correlated with protection from homologous simian-human immunodeficiency virus (SHIV) infection. The serum dilution that neutralized 50% of virus replication (ID50 titer) required to protect 90% of macaques was 1:364 against the challenge virus grown in primary rhesus CD4+ T cells. Structural analyses of vaccine-induced nAbs demonstrated targeting of the Env CD4 binding site or the N156 glycan and the third variable loop base. Autologous nAb specificities similar to those elicited in macaques by vaccination were isolated from the human living with HIV from which the CH505 Env immunogen was derived. CH505 viral isolates were isolated that mutated the V1 to escape both the infection-induced and vaccine-induced antibodies. These results define the specificities of a vaccine-induced nAb response and the protective titers of HIV-1 vaccine-induced nAbs required to protect nonhuman primates from low-dose mucosal challenge by SHIVs bearing a primary transmitted/founder Env.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

September 7, 2022

Volume

14

Issue

661

Start / End Page

eabo5598

Location

United States

Related Subject Headings

  • Vaccination
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Macaca mulatta
  • Immunization
  • Humans
  • HIV-1
  • Communicable Diseases
  • Antibodies, Viral
  • Antibodies, Neutralizing
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Saunders, K. O., Edwards, R. J., Tilahun, K., Manne, K., Lu, X., Cain, D. W., … Haynes, B. F. (2022). Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection. Sci Transl Med, 14(661), eabo5598. https://doi.org/10.1126/scitranslmed.abo5598
Saunders, Kevin O., Robert J. Edwards, Kedamawit Tilahun, Kartik Manne, Xiaozhi Lu, Derek W. Cain, Kevin Wiehe, et al. “Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection.Sci Transl Med 14, no. 661 (September 7, 2022): eabo5598. https://doi.org/10.1126/scitranslmed.abo5598.
Saunders KO, Edwards RJ, Tilahun K, Manne K, Lu X, Cain DW, et al. Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection. Sci Transl Med. 2022 Sep 7;14(661):eabo5598.
Saunders, Kevin O., et al. “Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection.Sci Transl Med, vol. 14, no. 661, Sept. 2022, p. eabo5598. Pubmed, doi:10.1126/scitranslmed.abo5598.
Saunders KO, Edwards RJ, Tilahun K, Manne K, Lu X, Cain DW, Wiehe K, Williams WB, Mansouri K, Hernandez GE, Sutherland L, Scearce R, Parks R, Barr M, DeMarco T, Eater CM, Eaton A, Morton G, Mildenberg B, Wang Y, Rountree RW, Tomai MA, Fox CB, Moody MA, Alam SM, Santra S, Lewis MG, Denny TN, Shaw GM, Montefiori DC, Acharya P, Haynes BF. Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection. Sci Transl Med. 2022 Sep 7;14(661):eabo5598.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

September 7, 2022

Volume

14

Issue

661

Start / End Page

eabo5598

Location

United States

Related Subject Headings

  • Vaccination
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Macaca mulatta
  • Immunization
  • Humans
  • HIV-1
  • Communicable Diseases
  • Antibodies, Viral
  • Antibodies, Neutralizing