Immunization with recombinant modified vaccinia virus Ankara can modify mucosal simian immunodeficiency virus infection and delay disease progression in macaques.
In the present study, the immunogenicity and protective efficacy of a recombinant vaccinia virus-based simian immunodeficiency virus (SIV) vaccine, given alone or in combination with a protein boost, were investigated. Cynomolgus macaques were immunized intramuscularly with modified vaccinia virus Ankara (MVA) expressing the SIVsm env and gag-pol genes (MVA-SIVsm) at 0 and 3 months (n=4), at 0, 3 and 8 months (n=4) or at 0 and 3 months followed by purified native SIVsm gp148 and recombinant SIVmac p27 in immunostimulatory complexes at 8 months (n=4). One month after the last immunization, the vaccinees, together with four naive control monkeys and four monkeys immunized with wild-type MVA, were challenged intrarectally with 10 MID50 SIVsm. At the time of challenge, antibody titres to SIV Env and lymphocyte proliferation responses to whole viral antigen were highest in vaccinees receiving MVA-SIVsm in combination with protein immunizations. Following rectal challenge, one of these vaccinees was completely protected. A prolonged survival time was observed in two of four monkeys in each of the groups immunized with MVA-SIVsm, in two monkeys given MVA-SIVsm followed by protein and in three of four monkeys given wild-type MVA, compared with naive controls. In conclusion, one monkey given the combined vaccine was protected completely against SIVsm infection. Furthermore, immunization with MVA-SIVsm, as well as wild-type MVA alone, seemed to delay disease progression after mucosal SIV infection in a proportion of the monkeys.
Nilsson
Charlotta
C
Swedish Institute for Infectious Disease Control and Microbiology and Tumor Biology Center, Karolinska Institute, SE-171 82 Solna, Sweden1.
Sutter
Gerd
G
Institute for Molecular Virology, GSF - National Research Centre for Environment and Health, Trogerstr. 4b, 81675 Munich, Germany2.
Walther-Jallow
Lilian
L
Swedish Institute for Infectious Disease Control and Microbiology and Tumor Biology Center, Karolinska Institute, SE-171 82 Solna, Sweden1.
Ten Haaft
Peter
P
Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands3.
Åkerblom
Lennart
L
Department of Virology, The National Veterinary Institute, Uppsala, Sweden4.
Heeney
Jonathan
J
Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands3.
Erfle
Volker
V
Institute for Molecular Virology, GSF - National Research Centre for Environment and Health, Trogerstr. 4b, 81675 Munich, Germany2.
Böttiger
Per
P
Swedish Institute for Infectious Disease Control and Microbiology and Tumor Biology Center, Karolinska Institute, SE-171 82 Solna, Sweden1.
Biberfeld
Gunnel
G
Swedish Institute for Infectious Disease Control and Microbiology and Tumor Biology Center, Karolinska Institute, SE-171 82 Solna, Sweden1.
Thorstensson
Rigmor
R
Swedish Institute for Infectious Disease Control and Microbiology and Tumor Biology Center, Karolinska Institute, SE-171 82 Solna, Sweden1.
D000285:Administration, Rectal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D007114:Immunization; D008252:Macaca fascicularis; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*
D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic