Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine.
Recombinant viruses hold promise as vectors for vaccines to prevent infectious diseases with significant global health impacts. One of their major limitations is that preexisting anti-vector neutralizing antibodies can reduce T cell responses to the insert antigens; however, the impact of vector-specific cellular immunity on subsequent insert-specific T cell responses has not been assessed in humans. Here, we have identified and compared adenovirus-specific and HIV-specific T cell responses in subjects participating in two HIV-1 vaccine trials using a vaccine vectored by adenovirus serotype 5 (Ad5). Higher frequencies of pre-immunization adenovirus-specific CD4⁺ T cells were associated with substantially decreased magnitude of HIV-specific CD4⁺ T cell responses and decreased breadth of HIV-specific CD8⁺ T cell responses in vaccine recipients, independent of type-specific preexisting Ad5-specific neutralizing antibody titers. Further, epitopes recognized by adenovirus-specific T cells were commonly conserved across many adenovirus serotypes, suggesting that cross-reactivity of preexisting adenovirus-specific T cells can extend to adenovirus vectors derived from rare serotypes. These findings provide what we believe to be a new understanding of how preexisting viral immunity may impact the efficacy of vaccines under current evaluation for prevention of HIV, tuberculosis, and malaria.
Vaccine and Infectious Disease Division and HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Nicole
N
Frahm
Allan C
AC
DeCamp
David P
DP
Friedrich
Donald K
DK
Carter
Olivier D
OD
Defawe
James G
JG
Kublin
Danilo R
DR
Casimiro
Ann
A
Duerr
Michael N
MN
Robertson
Susan P
SP
Buchbinder
Yunda
Y
Huang
Gregory A
GA
Spies
Stephen C
SC
De Rosa
M Juliana
MJ
McElrath
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics; D005822:Genetic Vectors; D015488:HIV Antigens / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012703:Serotyping; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D000956:Antigens, Viral; D015488:HIV Antigens; D014614:Vaccines, Synthetic