Maria Lemos
,
Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Anneta Naidoo
,
Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute, Cape Town, South Africa
Lamar Fleming
,
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Nonhlanhla Mkize
,
HIV Virology section, National Institute for Communicable Diseases, Johannesburg, South Africa
Rena Astronomo
,
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Hillary Mukudu
,
Khula Ndoda Mass Male Circumcision Project, Perinatal HIV Research Unit, Chris Hani-Baragwanath Academic Hospital, Johannesburg, South Africa
Limakatso Lebina
,
Khula Ndoda Mass Male Circumcision Project, Perinatal HIV Research Unit, Chris Hani-Baragwanath Academic Hospital, Johannesburg, South Africa
Sandie Thomson
,
Division of Gastroenterology, Groote Schuur Hospital, Cape Town, South Africa, Cape Town, South Africa
Neil Martinson
,
Khula Ndoda Mass Male Circumcision Project, Perinatal HIV Research Unit, Chris Hani-Baragwanath Academic Hospital, Johannesburg, South Africa
Christina Ochsenbauer
,
Department of Medicine and CFAR, University of Alabama at Birmingham, Birmingham, AL
Linda-Gail Bekker
,
The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Erica Andersen-Nissen
,
Cape Town HVTN Immunology Laboratory, Cape Town, Western Cape, South Africa
Lynn Morris
,
HIV Virology section, National Institute for Communicable Diseases, Johannesburg, South Africa
Julie McElrath
,
Department of Medicine, University of Washington, Seattle, WA
In non-human primate models, passive transfer of selected neutralizing antibodies against SIV have shown protection from repeated low dose rectal challenges. To estimate the functional concentrations required to prevent infection in humans, we have used the human colonic and foreskin explant models to test multiple antibodies and assess their ability to impair HIV infection in an ex-vivo system. We compared VRC01 (CD4 binding site), PG9 (V1V2 loop), PGT121 (V3 loop), 10e8 (MPER), PGT151 (trimer) that neutralize the tier 2 JRCSF virus at IC50 of 0.02-0.14 ug/ml in the TZM-bl assay. We show that antibody concentrations 10-50 times above the IC50 can prevent infection on colonic explants from 9 healthy South African donors. Antibody concentrations 5-10 times above the IC50 can prevent infection of foreskin explants from 14 healthy South African donors. The required antibody concentrations are dependent on mucosal activation levels, as addition of PHA significantly increases the antibody concentrations required for protection. Together, these results provide functional estimates of the concentrations of neutralizing antibodies required at site of viral entry in men, and provide a goal for both passive protection and HIV vaccine efforts in mucosal surfaces.
