The prime-boost strategies are promising AIDS vaccine methods for inducing potent immune responses (Excler J L, et al., 1997; Ramshaw I A, et al., 2000). Recently, this strategy has shown modest efficacy in preventing HIV infection by 31.2% compared with placebo in Thailand among more than 16, 000 volunteers (Rerks-Ngarm S, et al., 2009). Novel vaccination approaches, such as DNA vaccines and recombinant viral vector-based vaccines, have further expanded the scope of prime/boost strategies (Schneider J, et al., 1998; Hel Z, et al., 2001; Shiver J W, et al., 2002).
Wolff et al. first demonstrated that naked DNA plasmids can be taken up and expressed in mouse skeletal muscle cells (Wolff J A, et al., 1990). Since then, DNA injection has became a useful technique for expressing foreign proteins in mammalian cells. DNA vaccines are advantageous for their stability, in vivo expression which ensures that protein more closely resembles normal eukaryotic structure, with accompanying post-translational modification (Alarcon J B, et al., 1999), and antigen presentation by both MHC class I and MHC class Ⅱ molecules (Montgomery D L, et al., 1997; Robinson H L, et al., 2000). The main safety concern for DNA vaccines is plasmid integration. To date, few studies have been undertaken on the subject and most have concluded that there were no plasmid genomic integrations (Martin T, et al., 1999; Ledwith B J, et al., 2000; Vilalta A, et al., 2005). To detect rare DNA integration events, repeatanchored integration capture (RAIC)-PCR had been developed (Wang Z, et al., 2004). Random integrations of plasmid DNA into genomic DNA were detected (17 copies/μg genomic DNA, 50 μg plasmid inoculation) after intramuscular injection (Wang Z, et al., 2004). Therefore, efforts should still be made to enhance the safety of DNA vaccines in preclinical studies, such as reducing the frequency of immunization.
Recombinant vaccinia is considered as one of the most promising viral vectors because of its ability to induce long-lasting cellular responses against foreign antigen (Schneider J, et al., 1998; Hel Z, et al., 2001; Shiver J W, et al., 2002). In China, Tiantan vaccinia virus had most widely been utilized to eradicate smallpox (Zhao K, et al., 1995). Recombinant Tiantan vaccinia virus (rTV) has also been used as a vaccine vector against Epstein-Barr Virus (EBV) (Gu S, et al., 1991) and Hepatitis A virus (HAV) (Guo K J, et al., 1992) in human trials.
The DNA prime/rTV boost regimen reported previously consisted of a series of three vaccinations with DNA and a single boost with rTV (Ren L, et al., 2006; Huang X, et al., 2006). In this study, we explored a safer and effective DNA prime/rTV boost system, single DNA priming followed by a single rTV booster, for potential clinical trial as an AIDS vaccine.
Potent T cell Responses Induced by Single DNA Vaccine Boosted with Recombinant Vaccinia Vaccine
- Received Date: 06 January 2013
- Accepted Date: 06 March 2013
Abstract: Plasmid DNA, an effective vaccine vector, can induce both cellular and humoral immune responses. However, plasmid DNA raises issues concerning potential genomic integration after injection. This issue should be considered in preclinical studies. Tiantan vaccinia virus (TV) has been most widely utilized in eradicating smallpox in China. This virus has also been considered as a successful vaccine vector against a few infectious diseases. Potent T cell responses through T-cell receptor (TCR) could be induced by three injections of the DNA prime vaccine followed by a single injection of recombinant vaccinia vaccine. To develop a safer immunization strategy, a single DNA prime followed by a single recombinant Tiantan vaccinia (rTV) AIDS vaccine was used to immunize mice. Our data demonstrated that one DNA prime/rTV boost regimen induced mature TCR activation with high functional avidity, preferential T cell Vβ receptor usage and high sensitivity to anti-CD3 antibody stimulation. No differences in T cell responses were observed among one, two or three DNA prime/rTV boost regimens. This study shows that one DNA prime/rTV boost regimen is sufficient to induce potent T cell responses against HIV.