An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses.
The EuroVacc 02 phase I trial has evaluated the safety and immunogenicity of a prime-boost regimen comprising recombinant DNA and the poxvirus vector NYVAC, both expressing a common immunogen consisting of Env, Gag, Pol, and Nef polypeptide domain from human immunodeficiency virus (HIV)-1 clade C isolate, CN54. 40 volunteers were randomized to receive DNA C or nothing on day 0 and at week 4, followed by NYVAC C at weeks 20 and 24. The primary immunogenicity endpoints were measured at weeks 26 and 28 by the quantification of T cell responses using the interferon gamma enzyme-linked immunospot assay. Our results indicate that the DNA C plus NYVAC C vaccine regimen was highly immunogenic, as indicated by the detection of T cell responses in 90% of vaccinees and was superior to responses induced by NYVAC C alone (33% of responders). The vaccine-induced T cell responses were (a) vigorous in the case of the env response (mean 480 spot-forming units/10(6) mononuclear cells at weeks 26/28), (b) polyfunctional for both CD4 and CD8 T cell responses, (c) broad (the average number of epitopes was 4.2 per responder), and (d) durable (T cell responses were present in 70% of vaccinees at week 72). The vaccine-induced T cell responses were strongest and most frequently directed against Env (91% of vaccines), but smaller responses against Gag-Pol-Nef were also observed in 48% of vaccinees. These results support the development of the poxvirus platform in the HIV vaccine field and the further clinical development of the DNA C plus NYVAC C vaccine regimen.
Harari
Alexandre
A
Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
Bart
Pierre-Alexandre
PA
Stöhr
Wolfgang
W
Tapia
Gonzalo
G
Garcia
Miguel
M
Medjitna-Rais
Emmanuelle
E
Burnet
Séverine
S
Cellerai
Cristina
C
Erlwein
Otto
O
Barber
Tristan
T
Moog
Christiane
C
Liljestrom
Peter
P
Wagner
Ralf
R
Wolf
Hans
H
Kraehenbuhl
Jean-Pierre
JP
Esteban
Mariano
M
Heeney
Jonathan
J
Frachette
Marie-Joelle
MJ
Tartaglia
James
J
McCormack
Sheena
S
Babiker
Abdel
A
Weber
Jonathan
J
Pantaleo
Giuseppe
G
D016915:AIDS Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003062:Codon; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping; D006801:Humans; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D014612:Vaccines; D014765:Viral Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D016915:AIDS Vaccines; D003062:Codon; C078787:NYVAC vaccine; D010455:Peptides; D014612:Vaccines; D014765:Viral Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus