[13] ENHANCED EFFICACY OF VLP BASED DNA PRIME/PROTEIN BOOST IMMUNIZATION OF MACAQUES AGAINST PATHOGENIC SIMIAN IMMUNODEFICIENCY VIRUS (SIV) USING IL-12 AND GM-CSF ADJUVANTS

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] ENHANCED EFFICACY OF VLP BASED DNA PRIME/PROTEIN BOOST IMMUNIZATION OF MACAQUES AGAINST PATHOGENIC SIMIAN IMMUNODEFICIENCY VIRUS (SIV) USING IL-12 AND GM-CSF ADJUVANTS

[AUTHOR(S):] Kraiselburd E, Martinez I, Israel Z, Sidhu M, Villinger F, Montefiori D, Stout R
University Of Puerto Rico-MSC, San Juan, PR, USA

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 13

[Abstract:] Our studies investigated the potential for VecB7, a SIVsm DNA-based vaccine that produces virus-like particles (VLP) in vitro, to induce protective responses in rhesus macaques using a DNA prime/protein boost strategy. In addition, enhancement of antiviral immune responses was attempted by co-delivery of antigen with rhesus macaque IL-12 and GM-CSF as adjuvants. A group of 5 animals received 3 immunizations with 2mg VecB7 DNA together with DNA encoding the cytokine adjuvants (half DNA ID + half IM via Biojector), and were boosted with 500ug SIVsmB7 VLP plus 5ug/ml rec. rhesus IL-12 in alum. A control group (n=5) received empty VecB7 vector + DNA encoded adjuvants and were boosted with SIVsmB7 VLP + IL-12. Another control group (n=5) received no immunizations. The animals were challenged intrarectally with 105 TCID50 SIVsmE660 2 months after the final SIVsmB7 VLP boost. Prior to challenge, CTL against SIV Env and Gag were detected in only 1/5 vaccinees whereas neutralizing antibodies (Nab) were undetectable in all animals. With the exception of one vaccinee, all animals became infected post-challenge. The prime-boost regimen reduced peak viremia and plasma viral set point by >2 logs as compared to the naïve group (p<0.05). In the 4 infected vaccinees, plasma viral loads were below the detection threshold (500 vRNA copies/ml) from 8 wks post challenge to the current 18 wk time point. In contrast, the protein only vaccine control group showed viral loads surprisingly equal or higher than the naïve control group. Secondary Nab responses were noted against the vaccine strain, SIVsmH4, but not against SIVsmE660 in the vaccinees, while no secondary Nab responses were noted in naïve controls. The results indicate that IL-12/GM-CSF-augmented VLP-based DNA prime/protein boost vaccination induces protective immune responses against the replication of a pathogenic lentivirus and for the prevention of AIDS. The nature of the protective immune responses is under investigation.

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