~ Pergamon Int. J. lmmunopharmac., Vol. 19, No. 3, pp. 181-186, 1997 © 1997International Society for Immunopharrnacology Published by Elsevier Science Ltd. Printed in Great Britain 0192~0561/97 $17.00+ .00 PII: S0192-0561 (97)00018-0 KINETICS OF SPECIFIC SALIVARY IgA RESPONSES IN MAN AFTER ORAL CHALLENGE BY A RIBOSOMAL IMMUNOSTIMULANT MARIE N. KOLOPP-SARDA*$, MARIE C. BI~Nt~*,JEAN M. ALLAIREt, ANNE M. PERRUCHETt and GILBERT C. FAURE* *Laboratoire d'Immunologie; Facult6 de Mrdecine and CHU, Nancy, France; tCentre de Drveloppement Pierre Fabre, Labrge Innopole, Toulouse, France (Received 17 January 1997; revised 6 May 1997) Abstract--The kinetics of specific IgA mucosal responses was assessed in 12 healthy volunteers over 3 weeks of treatment by oral administration of an immunostimulant, Ribomunyl, composed of ribosomes from the four bacteria Streptococcus pyoyenes, Streptococcus pneumoniae, Klebsiella pneumoniae and Haernophilus influenzae. The levels of IgA specific for these four bacteria increased after each immunization and, after the third week of treatment, were significantly higher than baseline day 0 values. This study demonstrates that oral ribosomal immunostimulation results in the production of specificsalivary antibodies liable to recognize whole bacteria antigens, and therefore likely to confer protection. The kinetic analysis performed also demonstrates the rapidity of specific mucosal immune responses after oral stimulation in man, a feature still seldom explored. © 1997 International Society for Immunopharmacology. Keywords: salivary IgA, oral immunization, kinetics, ribosomal immunostimulant Oral vaccination, although seldom used, seems to be an appropriate approach to induce an effective pro- tection of mucosal areas. This is supported by the direct efficacy of the oral polio vaccine, and is sug- gested indirectly by the spontaneous protection against relapses conferred by upper respiratory tract or gastro-intestinal infections (Brandzaeg, 1992; Bloom & Boedeker, 1996). Recent physiological stud- ies of the mucosae-associated immune system have demonstrated that the mechanisms involved in this dynamic process of mucosal surface protection is driven by the antigenic stimulation taking place in Peyer's patches (PP). Antigens appear to be targeted to these structures, and the resulting activated specific B- and T-cells relocate in all areas of the mucosal system (Bienenstock, 1984; Kraehenbuhl & Neutra, 1992), where they achieve their terminal differ- entiation. During this process, part of the PP's acti- vated B-cells switch to IgA production, and release IgA upon completing their terminal differentiation into plasma-cells (McGhee & Kiyono, 1993). Through this mechanism, mucosal antigenic challenges result in the production of specific antibodies, mostly of the IgA isotype, in all secretions. The study of saliva therefore can provide information as to the efficacy of oral immunization. In order to achieve efficient mucosal responses, mat- uring individuals need repeated mucosal stimulations (Mestecky & McGhee, 1992). This seems to be the case with recurrent upper respiratory tract infections (URTI), numerous during childhood, that eventually become less and less frequent and nearly disappear as normal children grow up. In order to attain this degree of immune protection more readily, the classical approach of mucosal vaccination consists of using large doses of antigens, or supplementing vaccines with such adjuvants as ISCOMS (Immunostimulating Complexes), cholera toxin B or microparticles (Holmgren et al., 1993; Mowat et al., 1993; Maloy et al., 1994). Another approach involves using ribosomal prep- arations from potential pathogens. This type of ribosomal vaccine not only induces immune responses, but also confers efficient immune pro- tection (Youmans & Youmans, 1965; Gregory et al., 1986; Faure & Brnr, 1995). The objective of this study was to determine the kinetics of the mucosal immune response in man, after oral immunization using Ribomunyl, an oral riboso- mal immunostimulant. The immunological effect of this vaccine was assessed by measuring specific IgA responses in sequentially collected saliva samples. SAuthor to whom correspondence should be addressed at Laboratoire d'Immunologie, Facult6 de Mrdecine de Nancy, BP 184, 54500 Vandoeuvre les Nancy, France. Tel.: (33) 83 59 28 59; Fax: (33) 83 44 60 22; e-mail: bene@grip.u-nancy.fr 181