Evaluation of immunogenicity and efficacy of combined DNA and adjuvanted protein vaccination in a human immunodeficiency virus type 1/murine leukemia virus pseudotype challenge model.
A DNA plasmid encoding human immunodeficiency virus type 1 (HIV-1) env, nef and tat genes was used in mice in a prime-boost immunization regimen with the corresponding recombinant proteins. The genetic immunogen was delivered with a gene gun and the proteins were injected intramuscularly together with the adjuvant AS02A. Immunizations were followed by experimental challenge with pseudotyped HIV-1 subtype A or B virus. In an initial experiment in which animals were challenged four weeks after the final immunization, all single modality and prime-boost vaccinations resulted in a significant level of protection as compared to control animals. There was a trend for DNA-alone immunization yielding the highest protection. In a subsequent study, a late challenge was performed 19 weeks after the final immunization. All groups having received the DNA vaccine, either alone or in combination with adjuvanted protein, exhibited strong protection against HIV replication. The subtype-specific protection against the experimental HIV challenge was significantly stronger than the cross-protection. Cellular and humoral immune responses were assessed during immunization and after challenge, but without clear correlation to protection against HIV replication. The data suggest that either DNA or protein antigens alone provide partial protection against an HIV-1/MuLV challenge and that DNA immunization is essential for achieving very high levels of efficacy in this murine HIV-1 challenge model. While prime-boost combinations were more immunogenic than DNA alone, they did not appear to provide any further enhancement over DNA vaccine mediated efficacy. The DNA immunogen might prime low levels of CD8+ T cells responsible for virus clearance or possibly a yet unidentified mechanism of protection.
Rollman
Erik
E
Swedish Institute for Infectious Disease Control, Karolinska Institutet, Stockholm, Stockholm, Sweden.
Mathy
Nathalie
N
Bråve
Andreas
A
Boberg
Andreas
A
Kjerrström
Anne
A
van Wely
Cathy
C
Engström
Gunnel
G
Johansson
Susanne
S
Aperia
Kajsa
K
Eriksson
Lars E
LE
Benthin
Reinhold
R
Ertl
Peter
P
Heeney
Jonathan
J
Hinkula
Jorma
J
Voss
Gerald
G
Wahren
Britta
B
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D019470:Biolistics; D004195:Disease Models, Animal; D004338:Drug Combinations; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D009052:Leukemia Virus, Murine; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012192:Retroviridae Infections / Q000517:prevention & control*; D012503:Saponins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014412:Tumor Virus Infections / Q000517:prevention & control; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology
D016915:AIDS Vaccines; C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D015483:HIV Antibodies; D015488:HIV Antigens; D008050:Lipid A; D011994:Recombinant Proteins; D012503:Saponins; D019444:Vaccines, DNA; D022223:Vaccines, Subunit