Neutralizing antibodies and CD8+ T lymphocytes both contribute to immunity to adenovirus serotype 5 vaccine vectors.
The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. Ad5-specific neutralizing antibodies (NAbs) are thought to contribute substantially to anti-Ad5 immunity, but the potential importance of Ad5-specific T lymphocytes in this setting has not been fully characterized. Here we assess the relative contributions of Ad5-specific humoral and cellular immune responses in blunting the immunogenicity of a rAd5-Env vaccine in mice. Adoptive transfer of Ad5-specific NAbs resulted in a dramatic abrogation of Env-specific immune responses following immunization with rAd5-Env. Interestingly, adoptive transfer of Ad5-specific CD8(+) T lymphocytes also resulted in a significant and durable suppression of rAd5-Env immunogenicity. These data demonstrate that NAbs and CD8(+) T lymphocytes both contribute to immunity to Ad5. Novel adenovirus vectors that are currently being developed to circumvent the problem of preexisting anti-Ad5 immunity should therefore be designed to evade both humoral and cellular Ad5-specific immune responses.
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Shawn M
SM
Sumida
Diana M
DM
Truitt
Michael G
MG
Kishko
Janelle C
JC
Arthur
Shawn S
SS
Jackson
Darci A
DA
Gorgone
Michelle A
MA
Lifton
Wouter
W
Koudstaal
Maria G
MG
Pau
Stefan
S
Kostense
Menzo J E
MJ
Havenga
Jaap
J
Goudsmit
Norman L
NL
Letvin
Dan H
DH
Barouch
D000258:Adenovirus Infections, Human / Q000276:immunology* / Q000821:virology; D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005822:Genetic Vectors; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D012703:Serotyping; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; D014765:Viral Vaccines