CHILDHOOD VACCINES AND DENTAL CARIES IMMUNITY

Ada Forsyth Institute, Inc., Cambridge MA

Investigators

Linked publications & trials

Abstract

A principal long-term goal of the research conducted under DE-06153 is[unreadable] to develop a dental caries vaccine that mediates protection via the[unreadable] mucosal immune system. Corollary long-term objectives necessary to[unreadable] achieve this goal are (a) determine the age at which mucosal immune[unreadable] mechanisms are sufficiently mature to manifest potentially protective[unreadable] immune responses, (b) to identify mutants streptococcal components that[unreadable] are sufficiently immunogenic to elicit potentially protective immune[unreadable] responses prior to colonization with a cariogenic flora, and (c) to[unreadable] evaluate the capacity of immune elements within minor salivary gland[unreadable] tissue to function as inductive sites for potentially caries-protective[unreadable] antibody formation within the oral cavity. Although these long-term[unreadable] objectives are targeted for caries immunity, the resulting research[unreadable] should permit enhancement of secretory immunity for many infectious[unreadable] diseases that invade via mucosal routes.[unreadable] [unreadable] The research described in this application is intended first to reveal[unreadable] the capacity for secretory immunity at an age that is correlated with[unreadable] initial streptococcal infection. Secondly, the antigenic relationships[unreadable] and potential for protective immunity of two novel mutants streptococcal[unreadable] components (GBP Antigen) that are immunogenic at the time of initial[unreadable] mutants streptococcal infection will be identified. Thirdly, the ability[unreadable] of different minor salivary gland compartments to manifest secretory[unreadable] immune response after local induction with alum-associated and[unreadable] microencapsulated tetanus toxoid will be measured.[unreadable] These objectives will be explored by pursuing the following specific[unreadable] aims: (1) analysis of secretory immune responses of young children to[unreadable] components of proteins (tetanus toxoid), polysaccharide conjugate[unreadable] (capsular polysaccharide of Haemophilus influenza b), cellular[unreadable] (Bordetella pertussis), or intact attenuated viral vaccines (poliovirus)[unreadable] administered immediately prior to the critical period of mutans[unreadable] streptococcal infectivity; (2) determination of the ability of[unreadable] Streptococcus mutans 59 kDa glucan binding protein (GBP) to elicit immune[unreadable] responses that interfere with the colonization and cariogenicity of[unreadable] mutans streptococci in a rat model of dental caries; (3) purification,[unreadable] evaluation of epitopic distinctiveness, and potential for induction of[unreadable] protective immune responses by mutans streptococcal Antigen (the[unreadable] component to which the most frequent salivary immune responses are[unreadable] detected during the initial period of MS infectivity); and (4) analysis[unreadable] of topical immunization of minor salivary glands with respect to[unreadable] distribution of salivary responses within different minor gland[unreadable] microenvironments (lower, upper labial and palatine) with alum-associated[unreadable] and microencapsulated tetanus toxoid, used as an analogue of a protein-[unreadable] based dental caries vaccine.[unreadable]