Cross-clade neutralizing antibodies against HIV-1 induced in rabbits by focusing the immune response on a neutralizing epitope

Susan Zolla-Pazner; Sandra Cohen; Abraham Pinter; Chavdar Krachmarov; Terri Wrin; Shixia Wang; Shan Lu

doi:10.1016/j.virol.2009.05.039

Cross-clade neutralizing antibodies against HIV-1 induced in rabbits by focusing the immune response on a neutralizing epitope

Susan Zolla-Pazner, Sandra Cohen, Abraham Pinter, Chavdar Krachmarov, Terri Wrin, Shixia Wang, Shan Lu

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

Studies were performed to induce cross-clade neutralizing antibodies (Abs) by testing various combinations of prime and boost constructs that focus the immune response on structurally-conserved epitopes in the V3 loop of HIV-1 gp120. Rabbits were immunized with gp120 DNA containing a V3 loop characterized by the GPGR motif at its tip, and/or with gp120 DNA with a V3 loop carrying the GPGQ motif. Priming was followed by boosts with V3-fusion proteins (V3-FPs) carrying the V3 sequence from a subtype B virus (GPGR motif), and/or with V3 sequences from subtypes A and C (GPGQ motif). The broadest and most consistent neutralizing responses were generated when using a clade C gp120 DNA prime and with the V3_B-FP boost. Immune sera displayed neutralizing activity in three assays against pseudoviruses and primary isolates from subtypes A, AG, B, C, and D. Polyclonal Abs in the immune rabbit sera neutralized viruses that were not neutralized by pools of human anti-V3 monoclonal Abs. Greater than 80% of the neutralizing Abs were specific for V3, showing that the immune response could be focused on a neutralizing epitope and that vaccine-induced anti-V3 Abs have cross-clade neutralizing activity.

Original language	English
Pages (from-to)	82-93
Number of pages	12
Journal	Virology
Volume	392
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2009.05.039
State	Published - 15 Sep 2009
Externally published	Yes

Keywords

HIV-1
Immunization
Neutralizing antibodies
Pseudovirus
V3 loop
Vaccine
gp120

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10.1016/j.virol.2009.05.039

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title = "Cross-clade neutralizing antibodies against HIV-1 induced in rabbits by focusing the immune response on a neutralizing epitope",

abstract = "Studies were performed to induce cross-clade neutralizing antibodies (Abs) by testing various combinations of prime and boost constructs that focus the immune response on structurally-conserved epitopes in the V3 loop of HIV-1 gp120. Rabbits were immunized with gp120 DNA containing a V3 loop characterized by the GPGR motif at its tip, and/or with gp120 DNA with a V3 loop carrying the GPGQ motif. Priming was followed by boosts with V3-fusion proteins (V3-FPs) carrying the V3 sequence from a subtype B virus (GPGR motif), and/or with V3 sequences from subtypes A and C (GPGQ motif). The broadest and most consistent neutralizing responses were generated when using a clade C gp120 DNA prime and with the V3B-FP boost. Immune sera displayed neutralizing activity in three assays against pseudoviruses and primary isolates from subtypes A, AG, B, C, and D. Polyclonal Abs in the immune rabbit sera neutralized viruses that were not neutralized by pools of human anti-V3 monoclonal Abs. Greater than 80% of the neutralizing Abs were specific for V3, showing that the immune response could be focused on a neutralizing epitope and that vaccine-induced anti-V3 Abs have cross-clade neutralizing activity.",

keywords = "HIV-1, Immunization, Neutralizing antibodies, Pseudovirus, V3 loop, Vaccine, gp120",

author = "Susan Zolla-Pazner and Sandra Cohen and Abraham Pinter and Chavdar Krachmarov and Terri Wrin and Shixia Wang and Shan Lu",

note = "Funding Information: The authors wish to thank Drs. Arthur Nadas and Catarina Hioe for performing the statistical analyses and insightful discussions of the data. This work was supported by grants from the Bill and Melinda Gates Foundation, the National Institutes of Health (AI 36085 and AI 27742), and research funds from the Department of Veterans Affairs.",

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AU - Wrin, Terri

AU - Wang, Shixia

AU - Lu, Shan

N1 - Funding Information: The authors wish to thank Drs. Arthur Nadas and Catarina Hioe for performing the statistical analyses and insightful discussions of the data. This work was supported by grants from the Bill and Melinda Gates Foundation, the National Institutes of Health (AI 36085 and AI 27742), and research funds from the Department of Veterans Affairs.

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Cross-clade neutralizing antibodies against HIV-1 induced in rabbits by focusing the immune response on a neutralizing epitope

Abstract

Keywords

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