Intranasal vaccination against plague, tetanus and diphtheria

Abstract

Plague is an extremely virulent and potentially lethal infection caused by the bacterium Y. pestis. The current vaccine used to immunise against plague often fails to engender solid (100%) protection against inhalational infection with Y. pestis. Similarly, logistical factors favour the development of non-parenteral immunisation protocols to counter plague. Recently an improved parenteral vaccination strategy for plague, based on the recombinant subunit approach, has entered clinical trails. The Yersinia pestis subunit antigens (F1 and V) have been successfully incorporated into novel vaccine delivery systems such as biodegradable microspheres composed of poly-l-(lactide) (PLLA). Intranasal and intratracheal administration of PLLA microencapsulated F1 and V serves to protect experimental animals from inhalational and subcutaneous challenge with virulent Y. pestis bacilli. Liposomes have also been used to improve the immunogenicity of intranasally administered Y. pestis antigens, and the effectiveness of this approach to plague immunisation has been evaluated. Tetanus and diphtheria still cause many deaths worldwide. The maintenance of protective immunity to diphtheria and tetanus requires booster injections of the currently licensed toxoid vaccines. Consequently, many people remain unprotected. Improved coverage may well result from the development of effective non-invasive vaccines that could be readily distributed and potentially self-administered. To this end, the intranasal and inhalational routes of administration have been extensively investigated. Tetanus and diphtheria toxoids have been delivered intranasally to experimental animals using a wide variety of adjuvants (enterotoxin derivatives), penetration enhancers (cyclodextrins, bile salts, surfactants, cationic polymers) and delivery systems (microspheres and liposomes). As compared with parenteral vaccination, nasal immunisation has been shown favourably effective in small animal models, and a limited number of early phase clinical trails. As a caveat to this, adjuvantisation of toxoid/subunit molecules appears to be a requisite for elicitation of appreciable immunological responses, following nasal administration of acellular immunogens. Testing in larger animal models and humans is needed to ascertain if the promising results obtained in rodents can be reciprocated without compromising safety.