Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by preexisting poxvirus immunity

Abstract

Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vacciniaimmune BALB͞c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIVspecific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

Gene delivery to the lung using protein/polyethylenimine/plasmid complexes

“…Repeated dosing may thus require the use of different viral strains or different routes of administration. 2 Safety concerns can be an issue with attenuated viruses that have the potential to recombine and thus regain virulent properties, 3 and may also have directly detrimental effects in immunodeficient individuals. 4 Hence, there has been a great deal of interest in the development of nonviral vectors for gene therapy applications.…”

Generation and evaluation of a recombinant modified vaccinia virus Ankara vaccine for rabies

“…A recombinant MVA vaccine may still be of use if included in immunization schemes in the presence of maternally derived antibodies (for example against rabies virus) or in the presence of pre-existing immunity to vaccinia virus. These constructs might therefore have a potential for the vaccination of younger animals with maternally derived immunity or previously vaccinated animals that require boosting [70].…”

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

“…This supports the hypothesis that the level of protective immune responses elicited by an antigen can be influenced by the delivery vector; in this case, an attenuated HSV. Persistent effect after a single dose has also been observed with other attenuated, replication competent vaccine vectors and this property may translate into enhanced vaccine efficacy [52,67,68].…”