Prime-Boost Immunization with DNA Vaccine: Mucosal Route of Administration Changes the Rules

Abstract

In this study we assessed prime-boost immunization strategies with a DNA vaccine (gB DNA) and attenuated recombinant vaccinia virus vector (rvacgB), both encoding the gB protein of HSV, for their effectiveness at inducing mucosal as well as systemic immunity to HSV. Confirming the reports of others, systemic priming with gB DNA and systemic boosting with rvacgB were the most effective means of inducing serum Ab and splenic T cell responses. Nevertheless, the systemic prime-boost approach failed to induce detectable humoral or T cell responses at mucosal sites. However, such responses, at both proximal and distal locations, were induced if immunizations, especially the priming dose, were administered mucosally. Curiously, whereas optimal immunity with systemic priming and boosting occurred when gB DNA was used to prime and rvacgB was used as a boost, mucosal responses were optimal when animals were mucosally primed with rvacgB and boosted with gB DNA given mucosally. Furthermore, notable mucosal responses also occurred in animals mucosally primed with rvacgB and subsequently boosted systemically with gB DNA. Because the mucosal prime-boost immunization protocol also induced excellent systemic immune responses, the approach should be useful to vaccinate against agents for which both mucosal and systemic immunity are important for protection.

Development of a Vaccine against Murine Cytomegalovirus (MCMV), Consisting of Plasmid DNA and Formalin-Inactivated MCMV, That Provides Long-Term, Complete Protection against Viral Replication

“…6B), a key organ involved in viral transmission. We found with all three pDNA vaccines that further immunization with 10 7 PFU eq of FI-MCMV with alum generally resulted in protection greater than that elicited by 10 6 PFU eq with alum or by 10 7 PFU eq without alum. Importantly, four of four mice immunized with the All-U plasmid pool and with 10 7 PFU eq of FI-MCMV plus alum had undetectable levels in the salivary glands (Ͻ100 PFU/salivary gland).…”

Intranasal HIV-1-gp160-DNA/gp41 Peptide Prime-Boost Immunization Regimen in Mice Results in Long-Term HIV-1 Neutralizing Humoral Mucosal and Systemic Immunity

“…In addition, prime immunization with herpes simplex gB DNA and systemic boosting with rvacgB have been shown to be effective in inducing mucosal IgA responses in mucosally immunized mice, and these responses were increased when animals received the rvacgB as prime, followed by a booster of gB DNA (12). It is important to note that when we primed with synthetic gp41-CCR5 HIV-1 peptides and boosted with DNA/gp160-CCR5, the HIV-specific IgG or IgA Abs detected were nonneutralizing, and IgA-neutralizing Abs in the mucosa have been seen when mice were systemically primed with DNA and boosted with peptides.…”

“…Administration of DNA immunogens has been shown to be a potent alternative to induce cellular, although poor humoral, responses in mice and humans. Prime-booster immunization with DNA vaccine encoding the gp of herpes simplex virus (gB) 3 expressed and attenuated recombinant vaccinia virus vector (rvacgB) induced mucosal and systemic responses (12). DNA constructs encoding multi-CTL epitopes from human, macaques, and mice have also been administrated i.m., enhancing HIV-specific CTL epitopes (13).…”

Immunization with non-replicating E. coli minicells delivering both protein antigen and DNA protects mice from lethal challenge with lymphocytic choriomeningitis virus

“…There is mounting evidence to suggest that the administration of both DNA and the corresponding protein antigen vaccines, either sequentially or in combination, is more effective at generating robust immune responses [23][24][25]. Preliminary studies suggest that minicells codelivering a eukaryotic expression plasmid and the corresponding protein antigen could generate much higher antigen-specific serum IgG antibody responses when administered intramuscularly (i.m.)…”