Summary report: workshop on the potential risks of antibody-dependent enhancement in human HIV vaccine trials.
Concern that ADE of HIV infection could occur in vivo, as a result of HIV immunization, has arisen for several reasons. Immune-mediated disease enhancement occurs in several human and animal viral diseases, including lentiviral diseases. Tropism for host M/M cells is a common characteristic in these diseases. Sera from naturally infected, and possibly HIV-immunized, individuals have been shown to contain infection enhancing antibodies in vitro. Finally, there is considerable genetic, and potentially antigenic, diversity among HIV-1 isolates. This workshop was convened to evaluate these concerns regarding ADE of HIV infection in human HIV vaccine trials and to propose studies that would address this potential risk. Although there is currently no evidence that immune-mediated enhancement of disease occurs in HIV, there is clearly a need for carefully designed experiments to further evaluate this issue. As there are several notable diseases for which in vitro ADE does not correlate with ADE in vivo, in vitro data are insufficient to deter development of current HIV-1 vaccine candidates. In vivo correlates of protection/enhancement are necessary to evaluate the ADE risk accurately. The development of an HIV animal model that would allow testing of vaccine candidates is of primary importance.
Mascola
J R
JR
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850.
Mathieson
B J
BJ
Zack
P M
PM
Walker
M C
MC
Halstead
S B
SB
Burke
D S
DS
D016915:AIDS Vaccines / Q000009:adverse effects*; D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D004195:Disease Models, Animal; D014644:Genetic Variation; D006678:HIV / Q000235:genetics / Q000502:physiology; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D066298:In Vitro Techniques; D012307:Risk Factors; D014777:Virus Diseases / Q000209:etiology; D014779:Virus Replication / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies