This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the absence of an effective vaccine, other methods for preventing the sexual transmission of human immunodeficiency virus type 1 (HIV-1) must be pursued. To guide vaccine design, we assessed whether human monoclonal antibodies (MAbs) b12 and b6 against the CD4 binding site on HIV-1 gp120 and F240 against an immundominant epitope on gp41 could prevent vaginal transmission of SHIVSF162P4 to macaques. The two anti-gp120 MAbs have similar monomeric gp120-binding properties, measured in vitro, but b12 is strongly neutralizing while b6 is not. F240 is non-neutralizing. Applied vaginally at a high dose, the strongly neutralizing MAb b12 provided sterilizing immunity in 7/7 animals, b6 in 0/5 animals and F240 in 2/5 animals. Compared to control animals, the protection by b12 achieved statistical significance whereas that due to F240 did not. Additional passive transfer experiments also indicated that the ability of the administered anti-gp120 MAbs to neutralize the challenge virus was a critical influence on protection. Furthermore, there was a significant increase in the number of founder viruses establishing infection in animals receiving MAb b6, compared to other non-protected macaques. Thus a gp120-binding, non-neutralizing MAb against gp120 was, at best, completely ineffective at protection. Non-neutralizing antibodies to gp41 may have a limited capacity to protect, but the results suggest that the central focus of HIV-1 vaccine research should be on the induction of virus-neutralizing antibodies.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-50
Application #
8358104
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$57,750
Indirect Cost
Name
Tulane University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Robillard, Katelyn N; Lee, Kim M; Chiu, Kevin B et al. (2016) Glial cell morphological and density changes through the lifespan of rhesus macaques. Brain Behav Immun 55:60-69
Song, Ruijiang; Pace, Craig; Seaman, Michael S et al. (2016) Distinct HIV-1 Neutralization Potency Profiles of Ibalizumab-Based Bispecific Antibodies. J Acquir Immune Defic Syndr 73:365-373
Inglis, Fiona M; Lee, Kim M; Chiu, Kevin B et al. (2016) Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation. J Neurovirol 22:140-8
Liu, David X; Didier, Peter J; Plauche, Gail et al. (2016) Septicemia in an Indian Rhesus Macaque (Macaca mulatta) associated with Providencia stuartii. J Med Primatol 45:330-332
Lee, Kim M; Chiu, Kevin B; Sansing, Hope A et al. (2016) The flavivirus dengue induces hypertrophy of white matter astrocytes. J Neurovirol 22:831-839

Showing the most recent 10 out of 344 publications