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Anti-V2 Antibodies Virus Vulnerability Revealed by Envelope V1 Deletion in HIV Vaccine Candidates

87 Pages Posted: 21 Oct 2020 Publication Status: Published

See all articles by Isabela Silva de Castro

Isabela Silva de Castro

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Giacomo Gorini

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Rosemarie Mason

National Institutes of Health - Vaccine Research Center

Jason Gorman

National Institutes of Health - Vaccine Research Center

Massimiliano Bissa

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Mohammad Arif Rahman

National Cancer Institute - Immune Biology of Retroviral Infection Section

Anush Arakelyan

National Institutes of Health (NIH) - Section on Intercellular Interactions

Irene Kalisz

Advanced Bioscience Laboratories

Stephen Whitmey

Advanced Bioscience Laboratories

Manuel Becerra-Flores

New York University (NYU) - NYU Langone Health

Eric Ni

New York University (NYU) - NYU Langone Health

Kristina Peachman

Government of the United States of America - Henry M. Jackson Foundation for the Advancement of Military Medicine

Hung V. Trinh

Government of the United States of America - Henry M. Jackson Foundation for the Advancement of Military Medicine

Michael Read

Walter Reed Army Institute of Research - U.S. Military HIV Research Program

Mei-Hue Liu

National Institutes of Health (NIH) - Laboratory of Immunoregulation

Donald Van Ryk

National Institutes of Health (NIH) - Laboratory of Immunoregulation

Dominic Paquin-Proulx

Walter Reed Army Institute of Research - U.S. Military HIV Research Program

Zhanna Shubin

Government of the United States of America - Henry M. Jackson Foundation for the Advancement of Military Medicine

Marina Tuyishime

Duke University - Division of Surgical Sciences

Jennifer Peele

Duke University - Division of Surgical Sciences

Mohammed S. Ahmadi

National Institutes of Health (NIH) - Structural Biology Section

Raffaello Verardi

National Institutes of Health - Vaccine Research Center

Juliane Hill

National Institutes of Health (NIH) - ImmunoTechnology Section

Margaret Beddall

National Institutes of Health (NIH) - ImmunoTechnology Section

R. Nguyen

National Institutes of Health (NIH) - ImmunoTechnology Section

James Stamos

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Dai Fujikawa

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Susie Min

National Institutes of Health (NIH) - Laboratory of Immunoregulation

Luca Schifanella

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Monica Vaccari

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Veronica Galli

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Melvin N. Doster

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Namal PM Liyanage

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Sarkis Sarkis

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Francesca Caccuri

National Cancer Institute - Animal Models and Retroviral Vaccines Section

Celia LaBranche

Duke University - Department of Surgery

David C. Montefiori

Duke University - Division of Surgical Sciences

Georgia D. Tomaras

Duke University - Medical Center

Xiaoying Shen

Duke University - Duke Human Vaccine Institute

Margherita Rosati

National Cancer Institute at Frederick - Human Retrovirus Section

Barbara K. Felber

National Cancer Institute at Frederick - Human Retrovirus Pathogenesis Section

George N. Pavlakis

National Cancer Institute at Frederick - Human Retrovirus Section

David J. Venzon

National Cancer Institute - Biostatistics and Data Management Section

William Magnanelli

Frederick National Laboratory - AIDS and Cancer Virus Program

Matthew Breed

Frederick National Laboratory - AIDS and Cancer Virus Program

Josh Kramer

Frederick National Laboratory - AIDS and Cancer Virus Program

Brandon F. Keele

Frederick National Laboratory for Cancer Research - AIDS and Cancer Virus Program

Michael A. Eller

Walter Reed Army Institute of Research - U.S. Military HIV Research Program

Claudia Cicala

National Institutes of Health (NIH) - Laboratory of Immunoregulation

James Arthos

National Institutes of Health (NIH) - Laboratory of Immunoregulation

Guido Ferrari

Duke University - Division of Surgical Sciences

Leonid Margolis

National Institutes of Health (NIH) - Section on Intercellular Interactions

Marjorie Robert-Guroff

National Cancer Institute - Immune Biology of Retroviral Infection Section

Peter D. Kwong

National Institutes of Health - Vaccine Research Center

Mario Roederer

National Institutes of Health (NIH) - ImmunoTechnology Section

Mangala Rao

Walter Reed Army Institute of Research - U.S. Military HIV Research Program

Timothy J. Cardozo

New York University (NYU) - NYU Langone Health

Genoveffa Franchini

Medical University of Bialystok - Centre for Bioinformatics and Data Analysis

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Abstract

The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α4β7 integrin receptor. SIV vaccines engineered to delete V1 and favor an a-helix, rather than a β-sheet V2 conformation, enhanced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing a V2 in the β-sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.

Keywords: HIV, SIV, V1/V2, V1, ALVAC

Suggested Citation

Silva de Castro, Isabela and Gorini, Giacomo and Mason, Rosemarie and Gorman, Jason and Bissa, Massimiliano and Rahman, Mohammad Arif and Arakelyan, Anush and Kalisz, Irene and Whitmey, Stephen and Becerra-Flores, Manuel and Ni, Eric and Peachman, Kristina and Trinh, Hung V. and Read, Michael and Liu, Mei-Hue and Van Ryk, Donald and Paquin-Proulx, Dominic and Shubin, Zhanna and Tuyishime, Marina and Peele, Jennifer and Ahmadi, Mohammed S. and Verardi, Raffaello and Hill, Juliane and Beddall, Margaret and Nguyen, R. and Stamos, James and Fujikawa, Dai and Min, Susie and Schifanella, Luca and Vaccari, Monica and Galli, Veronica and Doster, Melvin N. and Liyanage, Namal PM and Sarkis, Sarkis and Caccuri, Francesca and LaBranche, Celia and Montefiori, David C. and Tomaras, Georgia D. and Shen, Xiaoying and Rosati, Margherita and Felber, Barbara K. and Pavlakis, George N. and Venzon, David J. and Magnanelli, William and Breed, Matthew and Kramer, Josh and Keele, Brandon F. and Eller, Michael A. and Cicala, Claudia and Arthos, James and Ferrari, Guido and Margolis, Leonid and Robert-Guroff, Marjorie and Kwong, Peter D. and Roederer, Mario and Rao, Mangala and Cardozo, Timothy J. and Franchini, Genoveffa, Anti-V2 Antibodies Virus Vulnerability Revealed by Envelope V1 Deletion in HIV Vaccine Candidates. Available at SSRN: https://ssrn.com/abstract=3699153 or http://dx.doi.org/10.2139/ssrn.3699153
This version of the paper has not been formally peer reviewed.

Isabela Silva de Castro

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Giacomo Gorini

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Rosemarie Mason

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Jason Gorman

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Massimiliano Bissa

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Mohammad Arif Rahman

National Cancer Institute - Immune Biology of Retroviral Infection Section ( email )

9609 Medical Center Drive
Rockville, MD 20850
United States

Anush Arakelyan

National Institutes of Health (NIH) - Section on Intercellular Interactions ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Irene Kalisz

Advanced Bioscience Laboratories ( email )

Stephen Whitmey

Advanced Bioscience Laboratories ( email )

Manuel Becerra-Flores

New York University (NYU) - NYU Langone Health ( email )

NY
United States

Eric Ni

New York University (NYU) - NYU Langone Health

NY
United States

Kristina Peachman

Government of the United States of America - Henry M. Jackson Foundation for the Advancement of Military Medicine ( email )

6720-A Rockledge Drive, Suite 100
Bethesda, MD 20817
United States

Hung V. Trinh

Government of the United States of America - Henry M. Jackson Foundation for the Advancement of Military Medicine ( email )

6720-A Rockledge Drive, Suite 100
Bethesda, MD 20817
United States

Michael Read

Walter Reed Army Institute of Research - U.S. Military HIV Research Program ( email )

Silver Spring, MD 20910
United States

Mei-Hue Liu

National Institutes of Health (NIH) - Laboratory of Immunoregulation ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Donald Van Ryk

National Institutes of Health (NIH) - Laboratory of Immunoregulation ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Dominic Paquin-Proulx

Walter Reed Army Institute of Research - U.S. Military HIV Research Program ( email )

Silver Spring, MD 20910
United States

Zhanna Shubin

Government of the United States of America - Henry M. Jackson Foundation for the Advancement of Military Medicine ( email )

6720-A Rockledge Drive, Suite 100
Bethesda, MD 20817
United States

Marina Tuyishime

Duke University - Division of Surgical Sciences ( email )

100 Fuqua Drive
Durham, NC 27708-0204
United States

Jennifer Peele

Duke University - Division of Surgical Sciences ( email )

100 Fuqua Drive
Durham, NC 27708-0204
United States

Mohammed S. Ahmadi

National Institutes of Health (NIH) - Structural Biology Section ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Raffaello Verardi

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Juliane Hill

National Institutes of Health (NIH) - ImmunoTechnology Section ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Margaret Beddall

National Institutes of Health (NIH) - ImmunoTechnology Section ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

R. Nguyen

National Institutes of Health (NIH) - ImmunoTechnology Section

9000 Rockville Pike
Bethesda, MD 20892
United States

James Stamos

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Dai Fujikawa

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Susie Min

National Institutes of Health (NIH) - Laboratory of Immunoregulation ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Luca Schifanella

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Monica Vaccari

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Veronica Galli

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Melvin N. Doster

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Namal PM Liyanage

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Sarkis Sarkis

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Francesca Caccuri

National Cancer Institute - Animal Models and Retroviral Vaccines Section ( email )

United States

Celia LaBranche

Duke University - Department of Surgery

Durham, NC 27715
United States

David C. Montefiori

Duke University - Division of Surgical Sciences

100 Fuqua Drive
Durham, NC 27715
United States

Georgia D. Tomaras

Duke University - Medical Center

100 Fuqua Drive
Durham, NC 27715
United States

Xiaoying Shen

Duke University - Duke Human Vaccine Institute ( email )

United States

Margherita Rosati

National Cancer Institute at Frederick - Human Retrovirus Section ( email )

Frederick, MD 21702
United States

Barbara K. Felber

National Cancer Institute at Frederick - Human Retrovirus Pathogenesis Section ( email )

Frederick, MD 21702
United States

George N. Pavlakis

National Cancer Institute at Frederick - Human Retrovirus Section ( email )

Frederick, MD 21702
United States

David J. Venzon

National Cancer Institute - Biostatistics and Data Management Section ( email )

9609 Medical Center Drive
Rockville, MD 20850
United States

William Magnanelli

Frederick National Laboratory - AIDS and Cancer Virus Program ( email )

Bethesda, MD 20892
United States

Matthew Breed

Frederick National Laboratory - AIDS and Cancer Virus Program ( email )

Bethesda, MD 20892
United States

Josh Kramer

Frederick National Laboratory - AIDS and Cancer Virus Program ( email )

Bethesda, MD 20892
United States

Brandon F. Keele

Frederick National Laboratory for Cancer Research - AIDS and Cancer Virus Program ( email )

Bethesda, MD 20892
United States

Michael A. Eller

Walter Reed Army Institute of Research - U.S. Military HIV Research Program

Silver Spring, MD 20910
United States

Claudia Cicala

National Institutes of Health (NIH) - Laboratory of Immunoregulation ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

James Arthos

National Institutes of Health (NIH) - Laboratory of Immunoregulation ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Guido Ferrari

Duke University - Division of Surgical Sciences

100 Fuqua Drive
Durham, NC 27715
United States

Leonid Margolis

National Institutes of Health (NIH) - Section on Intercellular Interactions ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Marjorie Robert-Guroff

National Cancer Institute - Immune Biology of Retroviral Infection Section ( email )

9609 Medical Center Drive
Rockville, MD 20850
United States

Peter D. Kwong

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Mario Roederer

National Institutes of Health (NIH) - ImmunoTechnology Section ( email )

Mangala Rao

Walter Reed Army Institute of Research - U.S. Military HIV Research Program ( email )

Silver Spring, MD 20910
United States

Timothy J. Cardozo

New York University (NYU) - NYU Langone Health ( email )

NY
United States

Genoveffa Franchini (Contact Author)

Medical University of Bialystok - Centre for Bioinformatics and Data Analysis ( email )

Poland

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