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223 Immunization against HIV-1 gp120 using SV40 as a Vaccine Delivery Vector
H. McKee and D. Strayer*
Jefferson Med. Coll., Philadelphia, PA, USA
Background: Among the most promising approaches to developing a vaccine against HIV-1 is the use of live viral vectors to deliver antigen-coding sequences in vivo, eliciting transgene-specific immune responses. Since recombinant SV40 vectors (rSV40) do not themselves elicit neutralizing responses, they can be used repeatedly to boost immune responses, enhancing both cell-mediated and humoral immune responses against a transgene product. We investigated whether rSV40s can be used as vectors to elicit immune responses against HIV-1 envelope glycoprotein gp120.
Methods: Two viral vectors (carrying HIV-1NL4-3 gp120) were used; a recombinant vaccinia virus (VCB41) and an rSV40 vector [SV(gp120)]. BALB/c mice were inoculated every 4 weeks and bled every 2 weeks. Sera were tested for gp120 binding activity using P815 cells infected with VCB41 as targets in a cell-based ELISA (CELISA). Gp120-specific cytotoxic T-cell (CTL) lysis was assayed by 51Cr-release assay using VCB41-infected P815 target cells and unselected splenic or popliteal lymph node (PLN) CTL. Immunization regimens using primary inoculation with VCB41 followed by boosting with SV(gp120), and SV(gp120) inoculation alone were compared.
Results: Immunization with SV(gp120) generated gp120-specific antibody responses in mice given as few as 2 inoculations. Additional immunizations, beyond a total of 3, did not significantly increase serum antibody levels. Similarly, high levels of gp120-specific CTL-mediated lysis of gp120-bearing P815 cells were seen after 3 inoculations with SV(gp120) (>60% specific lysis). Additional SV(gp120) injections maintained, but did not increase this level of specific lysis. Primary immunization with VCB41, followed by boosting with SV(gp120) was not more effective in eliciting either the humoral or cell-mediated responses, than was immunization with SV(gp120) alone.
Conclusions: Gp120-specific immune responses, particularly powerful CTL responses, can be elicited by immunization with an rSV40 vector encoding HIV-1 gp120. Immunization regimens using SV(gp120) alone elicit stronger immune responses than do regimens incorporating an inoculation with VCB41, followed by boosting with SV(gp120). This has implications for the potential use of rSV40 as a vaccine delivery vehicle against lentiviral antigens.
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