Immunological responses and viral modulatory effects of vaccination with recombinant modified vaccinia virus Ankara (rMVA) expressing structural and regulatory transgenes of simian immunodeficiency virus (SIVmac32H/J5M).
BACKGROUND
The immunogenicity and protective efficacy of recombinant modified vaccinia virus Ankara (rMVA) vectors expressing structural (gag/pol, env) and regulatory (tat, rev, nef) genes of SIVmac251/32H-J5 (rMVA-J5) were assessed.


METHODS
Immunization with rMVA constructs (2.5 x 10(7) IU) 32, 20 and 8 weeks pre-challenge was compared with 32 and 20 weeks but with a final boost 8 weeks pre-challenge with 2 x 10(6) fixed-inactivated HSC-F4 cells infected with SIVmac32H. Controls received rMVA vectors expressing an irrelevant transgene or were naïve challenge controls. All received 10 MID(50) SIVmac32H/J5 intravenously.


RESULTS
Vaccinates immunized with rMVA-J5 exhibited significant, albeit transient, control of peak primary viraemia despite inconsistent and variable immune responses elicted by vaccination. Humoral and cellular responses to Env were most consistent, with lower responses to Nef, Rev and Tat. Increasing titres of anti-vaccinia neutralizing antibodies reflected the number and dose of rMVA inoculations.


CONCLUSIONS
Improved combinations of viral vectors are required to elicit appropriate immune responses to control viral replication.
Berry
N
N
Division of Retrovirology, National Institute for Biological Standards and Control, South Mimms, UK. nberry@nibsc.ac.uk
Stebbings
R
R
Brown
S
S
Christian
P
P
Thorstensson
R
R
Ahmed
R K
RK
Davis
L
L
Ferguson
D
D
D'Arcy
N
N
Elsley
W
W
Hull
R
R
Lines
J
J
Wade-Evans
A
A
Stott
J
J
Almond
N
N
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005434:Flow Cytometry; D005822:Genetic Vectors; D017403:In Situ Hybridization; D008252:Macaca fascicularis / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019076:Transgenes / Q000235:genetics; D014611:Vaccination / Q000662:veterinary*; D014614:Vaccines, Synthetic / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology*; D014764:Viral Proteins / Q000378:metabolism
D000914:Antibodies, Viral; D012367:RNA, Viral; D014614:Vaccines, Synthetic; D014764:Viral Proteins