Intranasal vaccination against plague, tetanus and diphtheria

Plague is an extremely virulent and potentially lethal infection caused by the bacterium Y. pestis. The current vaccine used to immunise against plagu e often fails to engender solid (100%) protection against inhalational infe ction with Y. pestis. Similarly, logistical factors favour the development of non-parenteral immunisation protocols to counter plague. Recently an imp roved 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-(lac tide) (PLLA). Intranasal and intratracheal administration of PLLA microenca psulated FI 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 immunis ation has been evaluated. Tetanus and diphtheria still cause many deaths wo rldwide. The maintenance of protective immunity to diphtheria and tetanus r equires booster injections of the currently licensed toxoid vaccines. Conse quently, many people remain unprotected. Improved coverage may well result from the development of effective non-invasive vaccines that could be readi ly distributed and potentially self-administered. To this end, the intranas al and inhalational routes of administration have been extensively investig ated. Tetanus and diphtheria toxoids have been delivered intranasally to ex perimental animals using a wide variety of adjuvants (enterotoxin derivativ es), penetration enhancers (cyclodextrins, bile salts, surfactants, cationi c polymers) and delivery systems (microspheres and liposomes). As compared with parenteral vaccination, nasal immunisation has been shown favourably e ffective in small animal models, and a limited number of early phase clinic al trails. As a caveat to this, adjuvantisation of toxoid/subunit molecules appears to be a requisite for elicitation of appreciable immunological res ponses, following nasal administration of acellular immunogens. Testing in larger animal models and humans is needed to ascertain if the promising res ults obtained in rodents can be reciprocated without compromising safety. ( C) 2001 Elsevier Science B.V. All rights reserved.