Control of simian/human immunodeficiency virus viremia and disease progression after IL-2-augmented DNA-modified vaccinia virus Ankara nasal vaccination in nonhuman primates.
A successful HIV vaccine may need to stimulate antiviral immunity in mucosal and systemic immune compartments, because HIV transmission occurs predominantly at mucosal sites. We report here the results of a combined DNA-modified vaccinia virus Ankara (MVA) vaccine approach that stimulated simian/human immunodeficiency virus (SHIV)-specific immune responses by vaccination at the nasal mucosa. Fifteen male rhesus macaques, divided into three groups, received three nasal vaccinations on day 1, wk 9, and wk 25 with a SHIV DNA plasmid producing noninfectious viral particles (group 1), or SHIV DNA plus IL-2/Ig DNA (group 2), or SHIV DNA plus IL-12 DNA (group 3). On wk 33, all macaques were boosted with rMVA expressing SIV Gag-Pol and HIV Env 89.6P, administered nasally. Humoral responses were evaluated by measuring SHIV-specific IgG and neutralizing Abs in plasma, and SHIV-specific IgA in rectal secretions. Cellular responses were monitored by evaluating blood-derived virus-specific IFN-gamma-secreting cells and TNF-alpha-expressing CD8+ T cells, and blood- and rectally derived p11C tetramer-positive T cells. Many of the vaccinated animals developed both mucosal and systemic humoral and cell-mediated anti-SHIV immune responses, although the responses were not homogenous among animals in the different groups. After rectal challenge of vaccinated and naive animals with SHIV89.6P, all animals became infected. However a subset, including all group 2 animals, were protected from CD4+ T cell loss and AIDS development. Taken together, these data indicate that nasal vaccination with SHIV-DNA plus IL-2/Ig DNA and rMVA can provide significant protection from disease progression.
Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Frederic M N
FM
Bertley
Pamela A
PA
Kozlowski
Shainn-Wei
SW
Wang
Joseph
J
Chappelle
Jignesh
J
Patel
Oluwakemi
O
Sonuyi
Gail
G
Mazzara
David
D
Montefiori
Angela
A
Carville
Keith G
KG
Mansfield
Anna
A
Aldovini
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007376:Interleukin-2; D019444:Vaccines, DNA