Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model.
BACKGROUND
Current data suggest that an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine should elicit both adaptive humoral and cell mediated immune responses. Such a vaccine will also need to protect against infection from a range of heterologous viral variants. Here we have developed a simian-human immunodeficiency virus (SHIV) based model in cynomolgus macaques to investigate the breadth of protection conferred by HIV-1W61D recombinant gp120 vaccination against SHIVsbg and SHIVSF33 challenge, and to identify correlates of protection.


RESULTS
High titres of anti-envelope antibodies were detected in all vaccinees. The antibodies reacted with both the homologous HIV-1W61D and heterologous HIV-1IIIB envelope rgp120 which has an identical sequence to the SHIVsbg challenge virus. Significant titres of virus neutralising antibodies were detected against SHIVW61D expressing an envelope homologous with the vaccine, but only limited cross neutralisation against SHIVsbg, SHIV-4 and SHIVSF33 was observed. Protection against SHIVsbg infection was observed in vaccinated animals but none was observed against SHIVSF33 challenge. Transfer of immune sera from vaccinated macaques to naive recipients did not confer protection against SHIVsbg challenge. In a follow-up study, T cell proliferative responses detected after immunisation with the same vaccine against a single peptide present in the second conserved region 2 of HIV-1 W61D and HIV-1 IIIB gp120, but not SF33 gp120.


CONCLUSIONS
Following extended vaccination with a HIV-1 rgp120 vaccine, protection was observed against heterologous virus challenge with SHIVsbg, but not SHIVSF33. Protection did not correlate with serological responses generated by vaccination, but might be associated with T cell proliferative responses against an epitope in the second constant region of HIV-1 gp120. Broader protection may be obtained with recombinant HIV-1 envelope based vaccines formulated with adjuvants that generate proliferative T cell responses in addition to broadly neutralising antibodies.
Division of Retrovirology, HPA-NIBSC, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK. mark.page@nibsc.hpa.org.uk
Mark
M
Page
Richard
R
Stebbings
Neil
N
Berry
Robin
R
Hull
Deborah
D
Ferguson
Leanne
L
Davis
Laura
L
Duffy
William
W
Elsley
Joanna
J
Hall
Claire
C
Ham
Mark
M
Hassall
Bo
B
Li
Edward T
ET
Mee
Ruby
R
Quartey-Papafio
Nicola J
NJ
Rose
Nathalie
N
Mathy
Gerald
G
Voss
E James
EJ
Stott
Neil
N
Almond
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007106:Immune Sera / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D008252:Macaca fascicularis; D009500:Neutralization Tests; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007106:Immune Sera; D012367:RNA, Viral; D014614:Vaccines, Synthetic