Improved protection against simian immunodeficiency virus mucosal challenge in macaques primed with a DNA vaccine and boosted with the recombinant modified vaccinia virus Ankara and recombinant Semliki Forest virus

CEA, Service d'Immuno-Virologie, DSV, iMETI, 18 route du Panorama, Fontenay Aux Roses, France.
Vaccine (Impact Factor: 3.62). 02/2008; 26(4):532-45. DOI: 10.1016/j.vaccine.2007.11.025
Source: PubMed


Using the experimental infection of cynomolgus macaques with simian immunodeficiency virus (SIV) as a model of human immunodeficiency virus infection in humans, we studied the immunogenicity and protective efficacy of a vaccine strategy combining DNA, the modified recombinant vaccinia virus strain Ankara (MVA) and Semliki Forest virus (SFV) expressing gag, pol, env, tat, rev and nef from SIV. Although this immunization strategy induced moderate immune responses, the control of pathogenic SIVmac251 infection following mucosal challenge was clearly improved by vaccination. The viral load in vaccinated animals was reduced by 2 logs during the acute phase of infection and, in five of the six macaques, viral load fell below the detection limit at set point. No correlates of immune protection were identified, but SIV-specific T-cell responses were detected earlier in vaccinated animals than in controls. These results highlight the power of live attenuated virus vectors for vaccination strategies.

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    • "In subsequent years, the heterologous prime-boost vaccination regimen was adopted worldwide as a powerful means to elicit strong type 1 effector CD8 + T cell-mediated immune responses (Tc1) against viral, parasitic, and neoplastic antigens in rodents and non-human primates (NHP; Irvine et al., 1997; Amara et al., 2001; McShane et al., 2001; Zavala et al., 2001; Moore and Hill, 2004; Ellenberger et al., 2006; Gilbert et al., 2006; Aidoo et al., 2007; Nigam et al., 2007; Martinon et al., 2008; Sadagopal et al., 2008). "
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    • "Therefore, these vaccines could sustain cellular antigen expression and as a result, produce more antigenic protein than conventional naked DNA vaccines. RNA replicons may be derived from alphaviruses, Semilki Forest virus, or Sindbis virus, and can replicate in a wide range of cell types.62,63 Many replicons are designed to lack the structural genes, and thus noninfection particles are produced in the host and prevent the formation of neutralizing antibodies. "
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