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 × 107 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 × 106 fixed-inactivated HSC-F4 cells infected with SIVmac32H. Controls received rMVA vectors expressing an irrelevant transgene or were naive challenge controls. All received 10 MID50 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.