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M cell DNA vaccination for CTL immunity to HIV
Xinhai Wang1, David M Hone, Asmahan Haddad
1Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 22, 2003
Summary
Reovirus protein sigma1 effectively delivers DNA vaccines intranasally to induce HIV immunity. This method stimulates potent, long-lasting cellular immunity, outperforming naked DNA vaccines.
Area of Science:
- Immunology
- Vaccinology
- Molecular Biology
Background:
- Reovirus utilizes M cells for invasion, a characteristic adapted for vaccine delivery.
- Developing effective mucosal vaccines against HIV remains a significant challenge.
Purpose of the Study:
- To investigate the potential of reovirus protein sigma1 as a carrier for intranasal DNA vaccines against HIV.
- To evaluate the efficacy of a formulated DNA vaccine using protein sigma1 for inducing cell-mediated immunity.
Main Methods:
- Expression plasmids encoding HIV-1 envelope (Env) proteins were complexed with protein sigma1-poly-L-lysine.
- Formulated vaccines were administered intranasally to mice.
- Cell-mediated immunity, including cytotoxic T lymphocyte (CTL) responses and antiviral immunity, was assessed.
Main Results:
- The formulated gp160 DNA vaccine significantly enhanced Env-specific CTL responses in various tissues, including lungs and lymph nodes.
- Three doses were necessary for effective CTL induction, while intranasal naked DNA was ineffective.
- CTL activity peaked between weeks 8-10 and remained detectable by week 16.
- Vaccinated mice demonstrated antiviral immunity against vaccinia virus-env replication.
Conclusions:
- Protein sigma1-mediated intranasal DNA delivery is a promising alternative mucosal formulation for inducing cellular immunity against HIV-1.
- This approach elicits perforin- and Fas-dependent CTL responses producing IFN-gamma.
- The formulated vaccine offers a viable strategy compared to live viral vectors for mucosal immunization.