Redirecting the Humoral Immune Response againstStreptococcus mutansAntigen P1 with Monoclonal Antibodies

Abstract

The adhesin P1 of Streptococcus mutans has been studied as an anticaries vaccine antigen. An anti-P1 monoclonal antibody (MAb) bound to S. mutans prior to mucosal immunization of mice was shown previously to alter the amount, specificity, isotype, and biological activity of anti-P1 antibodies. The present study was undertaken to screen this and four additional anti-P1 MAbs for immunomodulatory activity when complexed with S. mutans and administered by a systemic route and to evaluate sera from immunized mice for the ability to inhibit adherence of S. mutans to immobilized human salivary agglutinin. All five MAbs tested influenced murine anti-P1 serum antibody responses in terms of subclass distribution and/or specificity. The effects varied depending on which MAb was used and its coating concentration. Two MAbs promoted a more effective, and two others a less effective, adherence inhibition response. An inverse relationship was observed between the ability of the MAbs themselves to inhibit adherence and the ability of antibodies elicited following immunization with immune complexes to inhibit adherence. Statistically significant correlations were demonstrated between the levels of anti-P1 serum immunoglobulin G2a (IgG2a) and IgG2b, but not of IgG1 or IgG3, and the ability of sera from immunized animals to inhibit bacterial adherence. These results indicate that multiple anti-P1 MAbs can mediate changes in the immune response and that certain alterations are potentially more biologically relevant than others. Immunomodulation by anti-P1 MAbs represents a useful strategy to improve the beneficial immune response against S. mutans.

Immunogenicity and In Vitro and In Vivo Protective Effects of Antibodies Targeting a Recombinant Form of the Streptococcus mutans P1 Surface Protein

“…Mice immunized with P1 39 -512 combined with adjuvants showed not only increased amounts of IgG1 but also larger amounts of IgG2a (alum and LT) and/or IgG2b (LT and FliC). Both IgG2a and IgG2b, but not IgG1, have been correlated with the antiadhesive activity of P1-specific antisera (49), suggesting that the efficacy of the antibodies would be affected by the incorporation of adjuvants. As expected, parenteral immunization of mice with the different vaccine formulations did not induce significant amounts of secretory IgA in saliva or feces (data not shown).…”

Antibody-Mediated Immunomodulation: a Strategy To Improve Host Responses against Microbial Antigens

“…IC of HBsAg and MAbs have been reported to stimulate proliferation of immune T lymphocytes more efficiently than did antigen alone (31), and promising therapeutic efficacy of an IC vaccine in the treatment of chronic hepatitis B patients has been reported (125,130). MAbs administered as part of IC have also been demonstrated to influence the humoral immune response against the P1 surface adhesin of the dental pathogen Streptococcus mutans (18,87,99,100). Both the specificity and the isotype of anti-P1 antibodies elicited in immunized mice were altered by the MAbs.…”

“…Due to negative feedback mechanisms, high levels of IgG antibodies have often been associated with inhibitory effects (50,53,104) but enhancing effects can also be observed depending on the nature of the antigen and the interaction of antibody within IC with inhibitory versus activating FcRs (51,104). Other factors reported to potentially, but not universally, influence outcome of immune responses have included antibody specificity (30,82,87), isotype (20,32,37,82), affinity (53), and route of administration (18,118).…”

“…It was not until P1 was subjected to partial proteolysis that a MAb-mediated shift in recognition of determinants contained in carboxy-versus amino-terminal fragments was demonstrated (18,100). The changes in specificity and efficacy of the elicited anti-P1 response varied depending on the P1 epitope recognized by five different immunomodulatory MAbs (87). Interestingly, MAbs that were themselves inhibitory of S. mutans adherence promoted a less effective adherence inhibition response, while MAbs that themselves did not inhibit bacterial adherence promoted the formation of antibodies that did.…”

Survey of the year 2004 commercial optical biosensor literature

“…In this group, researchers most often published data from IAsys (Affinity Sensors ), Spreeta and TISPR-1 (Texas Instruments [978][979][980][981][982][983][984][985][986][987][988][989][990][991][992] , small molecules , and cells, phage and virus particles [866][867][868][869][870][871][872][873][874][875][876][877][878][879][880][881][882][883][884][885]. In the applied sciences, biosensors increasingly contribute in clinical [886][887][888][889][890][891][892][893][894][895][896][897][898][899]…”