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Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.

Publication ,  Journal Article
Santra, S; Tomaras, GD; Warrier, R; Nicely, NI; Liao, H-X; Pollara, J; Liu, P; Alam, SM; Zhang, R; Cocklin, SL; Shen, X; Duffy, R; Xia, S-M ...
Published in: PLoS Pathog
August 2015
Published version (DOI) Open Access Copy (Duke) Link to item

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

Duke Scholars

Michael Anthony Moody
Author Michael Anthony Moody Pediatrics, Infectious Diseases
Georgia Doris Tomaras
Author Georgia Doris Tomaras Surgery, Surgical Sciences
Justin Joseph Pollara
Author Justin Joseph Pollara Surgery, Surgical Sciences
S. Munir Alam
Author S. Munir Alam Medicine, Duke Human Vaccine Institute
Xiaoying Shen
Author Xiaoying Shen Surgery, Surgical Sciences
Ryan Alexander Duffy
Author Ryan Alexander Duffy Medicine, General Internal Medicine
Moses Sekaran
Author Moses Sekaran Surgery, Surgical Sciences
David Charles Montefiori
Author David Charles Montefiori Surgery, Surgical Sciences
Feng Gao
Author Feng Gao Medicine, Infectious Diseases
Guido Ferrari
Author Guido Ferrari Surgery, Surgical Sciences
Barton Ford Haynes
Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute
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Published In

PLoS Pathog

DOI

10.1371/journal.ppat.1005042

EISSN

1553-7374

Publication Date

August 2015

Volume

11

Issue

8

Start / End Page

e1005042

Location

United States

Related Subject Headings

  • Virology
  • Viral Envelope Proteins
  • Surface Plasmon Resonance
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rectum
  • Protein Conformation
  • Macaca mulatta
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Santra, S., Tomaras, G. D., Warrier, R., Nicely, N. I., Liao, H.-X., Pollara, J., … Haynes, B. F. (2015). Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog, 11(8), e1005042. https://doi.org/10.1371/journal.ppat.1005042
Santra, Sampa, Georgia D. Tomaras, Ranjit Warrier, Nathan I. Nicely, Hua-Xin Liao, Justin Pollara, Pinghuang Liu, et al. “Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.” PLoS Pathog 11, no. 8 (August 2015): e1005042. https://doi.org/10.1371/journal.ppat.1005042.
Santra S, Tomaras GD, Warrier R, Nicely NI, Liao H-X, Pollara J, et al. Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog. 2015 Aug;11(8):e1005042.
Santra, Sampa, et al. “Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.” PLoS Pathog, vol. 11, no. 8, Aug. 2015, p. e1005042. Pubmed, doi:10.1371/journal.ppat.1005042.
Santra S, Tomaras GD, Warrier R, Nicely NI, Liao H-X, Pollara J, Liu P, Alam SM, Zhang R, Cocklin SL, Shen X, Duffy R, Xia S-M, Schutte RJ, Pemble Iv CW, Dennison SM, Li H, Chao A, Vidnovic K, Evans A, Klein K, Kumar A, Robinson J, Landucci G, Forthal DN, Montefiori DC, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Robb ML, Michael NL, Kim JH, Soderberg KA, Giorgi EE, Blair L, Korber BT, Moog C, Shattock RJ, Letvin NL, Schmitz JE, Moody MA, Gao F, Ferrari G, Shaw GM, Haynes BF. Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog. 2015 Aug;11(8):e1005042.

Published In

PLoS Pathog

DOI

10.1371/journal.ppat.1005042

EISSN

1553-7374

Publication Date

August 2015

Volume

11

Issue

8

Start / End Page

e1005042

Location

United States

Related Subject Headings

  • Virology
  • Viral Envelope Proteins
  • Surface Plasmon Resonance
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rectum
  • Protein Conformation
  • Macaca mulatta