Different patterns of immune responses but similar control of a simian-human immunodeficiency virus 89.6P mucosal challenge by modified vaccinia virus Ankara (MVA) and DNA/MVA vaccines.
Recently we demonstrated the control of a mucosal challenge with a pathogenic chimera of simian and human immunodeficiency virus (SHIV-89.6P) by priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia virus Ankara (DNA/MVA) vaccine. Here we evaluate the ability of the MVA component of this vaccine to serve as both a prime and a boost for an AIDS vaccine. The same immunization schedule, MVA dose, and challenge conditions were used as in the prior DNA/MVA vaccine trial. Compared to the DNA/MVA vaccine, the MVA-only vaccine raised less than 1/10 the number of vaccine-specific T cells but 10-fold-higher titers of binding antibody for Env. Postchallenge, the animals vaccinated with MVA alone increased their CD8 cell numbers to levels that were similar to those seen in DNA/MVA-vaccinated animals. However, they underwent a slower emergence and contraction of antiviral CD8 T cells and were slower to generate neutralizing antibodies than the DNA/MVA-vaccinated animals. Despite this, by 5 weeks postchallenge, the MVA-only-vaccinated animals had achieved as good control of the viral infection as the DNA/MVA group, a situation that has held up to the present time in the trial (48 weeks postchallenge). Thus, MVA vaccines, as well as DNA/MVA vaccines, merit further evaluation for their ability to control the current AIDS pandemic.
Amara
Rama Rao
RR
Vaccine Research Center and Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.
Villinger
Francois
F
Staprans
Silvija I
SI
Altman
John D
JD
Montefiori
David C
DC
Kozyr
Natalia L
NL
Xu
Yan
Y
Wyatt
Linda S
LS
Earl
Patricia L
PL
Herndon
James G
JG
McClure
Harold M
HM
Moss
Bernard
B
Robinson
Harriet L
HL
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D006678:HIV / Q000276:immunology / Q000472:pathogenicity; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D019444:Vaccines, DNA / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D015686:Gene Products, env; D015483:HIV Antibodies; D012367:RNA, Viral; D019444:Vaccines, DNA