Meningococcal infections*

Bull. Org. nmond. Sante 1971, 45, 291-293Bull. Wld Hlth Org.J Meningococcal Infections* 5. Duration of Polysaccharide-Vaccine- Induced Antibody MALCOLM S. ARTENSTEIN Serum antibodies induced in 12 volunteer subjects by injection ofgroup A and group C meningococcalpolysaccharide vaccines werefound topersistforperiods exceeding 14 months. Antibody response was measured by indirect haemagglutination and fluorescent antibody assays. Peak titres were reached in 2-8 weeks. Polysaccharide antigens appear to provide pro- longed stimulation of antibody levels in man. Most of the available data on group A and C meningo- coccal polysaccharide-induced antibodies have been obtained in US Army recruits and these studies have been limited to periods of 6-8 weeks (Arten- stein et al., 1970a; Gotschlich, Goldschneider & Artenstein, 1969b). This report presents antibody titres of laboratory volunteers up to 18 months following vaccination. MATERIALS AND METHODS Subjects consisted of laboratory personnel, 11 male and I female, between the ages of 25 and 45 years, who volunteered to receive vaccine. The vaccines consisted of purified meningococcal poly- saccharides prepared by the method of Gotschlich, Liu & Artenstein (1969a). Group C vaccines, lots C-4 and C-6, and group A, lot A-5, were pre- pared at the Walter Reed Army Institute of Research; lot C-7 was produced by the Squibb Institute for Medical Research. Doses of 50 pg were injected intradermally, subcutaneously, or by jet injector. Serum specimens were obtained at intervals and stored frozen at - 20°C until used. Nasopharyngeal cultures for meningococci were performed at the time of most of the venepunctures. None of the volunteers carried meningococcus of serogroups A or C during the period of observation and only one new carrier was detected. Serological studies utilized the indirect haemagglutination test in which human erythrocytes were sensitized with purified poly- saccharide antigens (Artenstein et al., 1970a). The fluorescent antibody test (FAB) was that described * From the Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, D.C., USA. by Goldschneider, Gotschlich & Artenstein (1969a). In the latter test fluorescein-conjugated rabbit anti- serum against heavy chain human IgG 1 was used. All sera from a given subject were assayed on the same day. RESULTS In 8 volunteers who received group C vaccines, haemagglutination titres increased significantly within 1 week following immunization and reached peak values (1: 128-1: 2048) between 2 and 8 weeks (see Table 1). Occasionally, titres fell several fold between 2 and 8 weeks. At 14-18 months after vaccination, 7 of the 8 subjects showed decreases of 2-8 tubes from the peak titre. The remaining volunteer (SB) had a titre at 18 months only 1 tube less than his peak titre at 8 weeks. Despite these changes, the geometric mean haemagglutination titre at 14-18 months was 1: 64 compared with <1: 2 prior to immunization. Antibody determined by immunofluorescence showed rising titres, which paralleled haemagglutin- ation titres but did not rise over 1: 256 in any subject; 3 of 5 subjects for whom 14- or 18-month data were available showed persistence of peak FAB titres. The other two subjects showed only 2 tube decreases from the peak. Only two individuals were known to be nasopharyngeal carriers at 18 months (29E serogroup). Of the 3 volunteers who showed FAB rises to vaccine lot A-5, titres remained very high throughout the 18 months of the study. All 4 individuals who received the group A vaccine showed significant haemagglutinating antibody response within 2 weeks, but the late sera were not studied by this test. 1 Supplied by Hyland Laboratories, Los Angeles, Calif., USA. 2727 - 291- M. S. ARTENSTEIN Table 1. Duration of antibodies induced by group A or group C polysaccharide vaccines Duration (weeks) b ° 1 4 16 c 8 64 C <2 C <2 8 <2 4 2 4 4 <2 32 8 128 32 32 <2 4 16 -2 256 2 64 64 c 64 64 c 32 1 024 HA-C -2 c Duration (months) b 8 _ 64 256 64 C 64 32 32 32 256 128 32 128 128 512 256 64 256 256 128 128 64 256 5 128 32 64 32 1 024 8 12 14 17-18 128 128 64 64 64 64 64 32 c 256 16 8 256 128 64 16 64 128 256C 64 64 64 64 a id = Intradermal; sc = subcutaneous; jet = jet injection. b Values are reciprocals of serum titres. c Meningococcal carrier. DISCUSSION Previous reports of antibody response to the purified group A and C polysaccharide vaccines in volunteers showed that haemagglutinating, FAB, and bactericidal antibody titres remained essentially unchanged from the peak values for periods of 20-37 weeks after vaccination (Artenstein et al., 1970a; Gotschlich, Goldschneider & Artenstein, 1969b). Roberts (1970) showed that serum opsonins persisted for as long as 14 months after meningo- coccal polysaccharide immunization. Heidelberger et al. (1946), studying the antibody response to type-specific pneumococcal polysaccharides, found that antibody levels (measured by precipitable anti- body nitrogen) persisted almost unchanged for 8 months. His volunteers were reinjected at that time but failed to show antibody increase. Sub- sequently, titres declined slowly and at 2 years from the initial injection averaged one-tenth to one-half of the maximum antibody content. Attempts to stimulate antibody response with reinjection of meningococcal group C polysaccharides (Artenstein et al., 1970a) have also been unsuccessful. The relationship of haemagglutinating and FAB antibodies to immunity from systemic infection deserves some comment. Antipolysaccharide anti- body as determined by the haemagglutination test is group specific (Gotschlich, Goldschneider & Arten- stein, 1969b). Although the FAB test using whole organisms as antigens detects antibodies cross- reactive with other meningococci (Goldschneider, Volun- Route a teer BLB id HS id CH id JS id WBR Sc JD sc WBA sc JL id SB id PE id DU id Vaccine A-5 C-7 C-6 C-4 Assay FAB-A FAB-A FAB-A FAB-A FAB-C HA-C FAB-C HA-C FAB-C HA-C FAB-C HA-C FAB-C HA-C FAB -C HA-C FAB-C HA-C FT jet 292 MENINGOCOCCAL INFECTIONS. 5 293 Gotschlich & Artenstein, 1969b), following specific polysaccharide immunization the FAB response is group-specific (Gotschlich, Goldschneider & Arten- stein, 1969b). As shown by Goldschneider, Gotsch- lich & Artenstein (1969b), antibody directed against the group C polysaccharide constitutes the bulk of bactericidal antibody to group C meningococci in many human sera. Since bactericidal antibodies are lacking in individuals who are highly susceptible to systemic meningococcal infection and they are present in the serum of the great majority of recruits who escape disease (Goldschneider, Gotschlich & Artenstein, 1969a) it is inferred that the anti- bodies are protective. The ability of the group A and C polysaccharide vaccines to stimulate the production of group-specific antipolysaccharide antibodies, which are of long duration, suggests strongly that protection trom bacteraemia will also be durable. The volunteers in the present study were all laboratory personnel engaged in meningococcal research; in addition, some were heavily exposed to recruit carriers during the course of culture surveys. The antibody data presented must, therefore, be cautiously interpreted and confirmation of these results in other populations is desirable. RtSUME' INFECTIONS MENINGOCOCCIQUES: 5. PERSISTANCE DES ANTICORPS SUSCITI-Sfl PAR DES VACCINS POLYSACCHARIDIQUES On a utilise 1'epreuve d'hemagglutination indirecte et le test des anticorps fluorescents pour mesurer la reponse immunitaire chez 12 volontaires vaccines a I'aide de vaccins antimeningococciques contenant des antigenes polysaccharidiques des groupes A ou C. L'evolUtion serologique a e suivie pendant 18 mois. Les titres ont atteint leur valeur maximale 2 a 8 semaines apres la vaccination. Chez les sujets vaccines par des anti- genes du groupe C, ils ont d6cru legerement entre le 14e et le 18e mois, mais se sont maintenus a un niveau nette- ment superieur au niveau pr6vaccinal. Pendant les 18 mois de 1'etude, les anticorps des groupes A et C deceles par l'immunofluorescence n'ont pr6sente que de faibles variations de leur titre par rapport aux titres maximaux. ACKNOWLEDGEMENTS Dr E. C. Tramont. Dr W. C. Branche, Jr, Miss H. Fleet, and Mr. C Harkin sprovided,excellent technical assistance. REFERENCES Artenstein, M. S., Gold, R., Zimmerly, J. G., Wyle, F. A., Branche, W. C. & Harkins, C. (1970a) J. infect. Dis., 121, 372-377 Artenstein, M. S., Gold, R., Zimmerly, J. G., Wyle, F. A., Schneider, H. & Harkins, C. (1970b) New Eng. J. Med., 282, 417420 Goldschneider, I., Gotschlich, E. C. & Artenstein, M. S. (1969a) J. exp. Med., 129, 1307-1326 Goldschneider, I., Gotschlich, E. C. & Artenstein, M. S. (1969b) J. exp. Med., 129, 1327-1348 Gotschlich, E. C., Liu, T. Y. & Artenstein, M. D. (1969a) J. exp. Med., 129 1349-1365 Gotschlich, E. C., Goldschneider, I. & Artenstein, M. S. (1969b) J. exp. Med., 129, 1367-1384 Heidelberger, M., MacLeod, C. M., Kaiser, S. J. & Robinson, B. (1946) J. exp. Med., 83, 303-320 Roberts, R. B. (1970) J. exp. Med., 131, 499-513