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Title: Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site

Journal Article · · Cell Reports
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  1. Duke Univ. School of Medicine, Durham, NC (United States)
  2. Harvard Medical School, Boston, MA (United States)
  3. National Inst. for Communicable Diseases, Johannesburg (South Africa); Univ. of the Witwatersrand, Johannesburg (South Africa)
  4. Univ. of KwaZulu-Natal, Durban (South Africa); Columbia Univ., New York, NY (United States)
  5. Novartis Vaccines and Diagnostics, Inc., Cambridge, MA (United States)
  6. Boston Univ., MA (United States)
  7. National Inst. for Communicable Diseases, Johannesburg (South Africa); Univ. of KwaZulu-Natal, Durban (South Africa); Univ. of the Witwatersrand, Johannesburg (South Africa)
  8. Harvard Medical School, Boston, MA (United States); Howard Hughes Medical Inst., Boston, MA (United States)
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Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
NIH/NIAID/DAIDS
Grant/Contract Number:
1F32AI116355-01
OSTI ID:
1234757
Journal Information:
Cell Reports, Vol. 14, Issue 1; ISSN 2211-1247
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 39 works
Citation information provided by
Web of Science

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Cited By (16)

Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies journal January 2017
Advances in HIV-1 Vaccine Development journal April 2018
Native-like Env trimers as a platform for HIV-1 vaccine design journal January 2017
Induction of Heterologous Tier 2 HIV-1-Neutralizing and Cross-Reactive V1/V2-Specific Antibodies in Rabbits by Prime-Boost Immunization journal July 2016
Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates journal February 2018
HIV-1 immunogens and strategies to drive antibody responses towards neutralization breadth journal November 2018
Somatic hypermutation to counter a globally rare viral immunotype drove off-track antibodies in the CAP256-VRC26 HIV-1 V2-directed bNAb lineage journal September 2019
Quantification of the Resilience and Vulnerability of HIV-1 Native Glycan Shield at Atomistic Detail journal January 2020
RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses journal October 2018
Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies journal August 2016
Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth journal October 2018
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity journal October 2016
Brief introduction of current technologies in isolation of broadly neutralizing HIV-1 antibodies journal January 2018
Identification and specificity of broadly neutralizing antibodies against HIV journal January 2017
Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs journal July 2018
Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial journal February 2017

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