Protection against pneumonic plague following oral immunization with a non-replicating vaccine

Abstract

Yersinia pestis is a dangerous bacterial pathogen that when inhaled can rapidly induce fatal pneumonic plague. Thus, there is a need for stable, safe, and easily administered mucosal vaccines capable of eliciting effective protection against pulmonary Y. pestis infections. Cationic liposome–nucleic acid complexes (CLDC) have been shown previously to be effective vaccine adjuvants for parenteral immunization, but have not been previously evaluated for use in oral immunization. Therefore, we investigated the ability of an orally administered CLDC adjuvanted vaccine to elicit protective immunity against lethal pneumonic plague. C57Bl/6 mice were vaccinated orally or subcutaneously using 10 μg Y. pestis F1 antigen combined with CLDC and immune responses and protection from challenge was assessed. We found that oral immunization elicited high titers of anti-F1 antibodies, equivalent to those generated by parenteral immunization. Importantly, orally immunized mice were protected from lethal pulmonary challenge with virulent Y. pestis for up to 18 weeks following vaccination. Vaccine-induced protection following oral immunization was found to be dependent primarily on CD4+ T cells, with a partial contribution from CD8+ T cells. Thus, CLDC adjuvanted vaccines represent a new type of orally administered, non-replicating vaccine capable of generating effective protection against pulmonary infection with virulent Y. pestis.

Mucosal immunization with liposome-nucleic acid adjuvants generates effective humoral and cellular immunity

“…For example, we have recently reported that oral administration of CLDC-adjuvanted vaccines is also capable of generating substantial protective immunity against pulmonary challenge with Yersinia pestis [87]. Thus, induction of efficient mucosal immunity, particularly at pulmonary surfaces, appears to be a general property of CLDC-based adjuvants.…”

Plague: Infections of Companion Animals and Opportunities for Intervention

“…With a view to oral administration of the vaccine, the F1-V fusion has been expressed in transgenic plants and fruit and was demonstrated to be immunogenic by oral or sub-cutaneous delivery [70-72], and the expression of the F1 and V antigens by attenuated Salmonella strains dosed orally has been demonstrated to protect mice from bubonic plague [73,74]. Oral immunisation of mice with F1 and V antigens formulated in an amphipathic oily emulsion [75], or in cationic liposome-nucleic acid complexes (CLDC) combined with F1 antigen, has also been shown to protect mice partially or fully against pneumonic plague [76]. …”

Plague Vaccine Development: Current Research and Future Trends

“…Microencapsulation (62) and lipid A mimetics (63) of recombinant LcrV–F1 fusion protein induced a mixed Th1/Th2 cell-mediated immune response and provided protection against pneumonic plague in mice and rats. Liposome, such as cationic liposome nucleic acid complexes (64), and proteosomes, such as protollin (65), have been evaluated with F1–LcrV and have been shown to protect against pneumonic plague.…”