Abstract
Pneumococcal type 9V polysaccharide (PS), contained in the current pneumococcal vaccine, induces only a weak antibody response in young children and therefore is not an effective vaccine for young children. To increase its immunogenicity, a conjugate of PS to a protein carrier, tetanus toxoid (TT), was prepared. To quantify the immune response, mouse anti-9V PS immunoglobulin G (IgG) and IgM reference standards were established. Young mice immunized at 2 weeks of age produced IgM antibody in response to 9V PS alone or 9V PS conjugated to TT. However, only the 9V PS-TT conjugate induced an IgG antibody response and an anamnestic effect. Thus, a covalent linkage between TT and 9V PS was required for isotype switching from IgM to IgG. 9V PS-TT adsorbed with aluminum hydroxide adjuvant resulted in a fivefold or greater increase in the IgG antibody level. We also studied the effect of maternal immunization on the immune response of young mice to 9V PS-TT. Maternal immunization before mating or before mating and during gestation primed 2-week-old progeny given two injections of 9V PS-TT to produce more IgM antibody than progeny from unimmunized mothers. The IgG antibody level of neonates at birth was similar to that observed in the mothers and was probably passive antibody. These results indicate that maternal immunization with an optimum dose of a PS-protein conjugate before and/or during pregnancy, followed by immunization of the offspring with the conjugate, could provide young children with an enhanced IgM antibody response to pneumococcal PSs.
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Selected References
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- AUSTRIAN R., GOLD J. PNEUMOCOCCAL BACTEREMIA WITH ESPECIAL REFERENCE TO BACTEREMIC PNEUMOCOCCAL PNEUMONIA. Ann Intern Med. 1964 May;60:759–776. doi: 10.7326/0003-4819-60-5-759. [DOI] [PubMed] [Google Scholar]
- Aaberge I. S., Michaelsen T. E., Heier H. E. IgG subclass antibody responses to pneumococcal polysaccharide vaccine in splenectomized, otherwise normal, individuals. Scand J Immunol. 1990 Jun;31(6):711–716. doi: 10.1111/j.1365-3083.1990.tb02822.x. [DOI] [PubMed] [Google Scholar]
- Anderson P., Pichichero M. E., Insel R. A. Immunization of 2-month-old infants with protein-coupled oligosaccharides derived from the capsule of Haemophilus influenzae type b. J Pediatr. 1985 Sep;107(3):346–351. doi: 10.1016/s0022-3476(85)80504-7. [DOI] [PubMed] [Google Scholar]
- Austrian R. Pneumococcal polysaccharide vaccines. Rev Infect Dis. 1989 May-Jun;11 (Suppl 3):S598–S602. doi: 10.1093/clinids/11.supplement_3.s598. [DOI] [PubMed] [Google Scholar]
- Baker C. J., Rench M. A., Edwards M. S., Carpenter R. J., Hays B. M., Kasper D. L. Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus. N Engl J Med. 1988 Nov 3;319(18):1180–1185. doi: 10.1056/NEJM198811033191802. [DOI] [PubMed] [Google Scholar]
- Barrett D. J., Lee C. G., Ammann A. J., Ayoub E. M. IgG and IgM pneumococcal polysaccharide antibody responses in infants. Pediatr Res. 1984 Nov;18(11):1067–1071. doi: 10.1203/00006450-198411000-00001. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Braley-Mullen H. Antigen requirements for priming of IgG producing B memory cells specific for Type III pneumococcal polysaccharide. Immunology. 1980 Aug;40(4):521–527. [PMC free article] [PubMed] [Google Scholar]
- Briles D. E., Horowitz J., McDaniel L. S., Benjamin W. H., Jr, Claflin J. L., Booker C. L., Scott G., Forman C. Genetic control of the susceptibility to pneumococcal infection. Curr Top Microbiol Immunol. 1986;124:103–120. doi: 10.1007/978-3-642-70986-9_7. [DOI] [PubMed] [Google Scholar]
- Douglas R. M., Miles H. B. Vaccination against Streptococcus pneumoniae in childhood: lack of demonstrable benefit in young Australian children. J Infect Dis. 1984 Jun;149(6):861–869. doi: 10.1093/infdis/149.6.861. [DOI] [PubMed] [Google Scholar]
- Fischer G. W., Hemming V. G., Gloser H. P., Bachmayer H., von Pilar C. E., Wilson S. R., Baron P. A. Polyvalent group B streptococcal immune globulin for intravenous administration: overview. Rev Infect Dis. 1990 May-Jun;12 (Suppl 4):S483–S491. doi: 10.1093/clinids/12.supplement_4.s483. [DOI] [PubMed] [Google Scholar]
- Gill T. J., 3rd, Kunz H. W. Enhanced antibody response in the offspring of immunized rats. J Immunol. 1971 Jan;106(1):274–275. [PubMed] [Google Scholar]
- Gill T. J., 3rd, Repetti C. F., Metlay L. A., Rabin B. S., Taylor F. H., Thompson D. S., Cortese A. L. Transplacental immunization of the human fetus to tetanus by immunization of the mother. J Clin Invest. 1983 Sep;72(3):987–996. doi: 10.1172/JCI111071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillespie S. H. Aspects of pneumococcal infection including bacterial virulence, host response and vaccination. J Med Microbiol. 1989 Apr;28(4):237–248. doi: 10.1099/00222615-28-4-237. [DOI] [PubMed] [Google Scholar]
- Insel R. A. Maternal immunization to prevent neonatal infections. N Engl J Med. 1988 Nov 3;319(18):1219–1220. doi: 10.1056/NEJM198811033191809. [DOI] [PubMed] [Google Scholar]
- Istre G. R., Tarpay M., Anderson M., Pryor A., Welch D. Invasive disease due to Streptococcus pneumoniae in an area with a high rate of relative penicillin resistance. J Infect Dis. 1987 Nov;156(5):732–735. doi: 10.1093/infdis/156.5.732. [DOI] [PubMed] [Google Scholar]
- Jennings H. J. Capsular polysaccharides as vaccine candidates. Curr Top Microbiol Immunol. 1990;150:97–127. doi: 10.1007/978-3-642-74694-9_6. [DOI] [PubMed] [Google Scholar]
- Lawrence E. M., Edwards K. M., Schiffman G., Thompson J. M., Vaughn W. K., Wright P. F. Pneumococcal vaccine in normal children. Primary and secondary vaccination. Am J Dis Child. 1983 Sep;137(9):846–850. doi: 10.1001/archpedi.1983.02140350024007. [DOI] [PubMed] [Google Scholar]
- Lee C. J., Banks S. D., Li J. P. Virulence, immunity, and vaccine related to Streptococcus pneumoniae. Crit Rev Microbiol. 1991;18(2):89–114. doi: 10.3109/10408419109113510. [DOI] [PubMed] [Google Scholar]
- Lee C. J., Ching E. D., Vickers J. H. Maternal immunity and antibody response of neonatal mice to pneumococcal type 19F polysaccharide. J Clin Microbiol. 1991 Sep;29(9):1904–1909. doi: 10.1128/jcm.29.9.1904-1909.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee C. J., Lin K. T. Studies on vaccine control and immunogenicity of polysaccharides of Streptococcus pneumoniae. Rev Infect Dis. 1981 Mar-Apr;3 (Suppl):S51–S60. doi: 10.1093/clinids/3.supplement_1.s51. [DOI] [PubMed] [Google Scholar]
- Lee C. J., Takaoka Y., Saito T. Maternal immunization and the immune response of neonates to pneumococcal polysaccharides. Rev Infect Dis. 1987 May-Jun;9(3):494–510. doi: 10.1093/clinids/9.3.494. [DOI] [PubMed] [Google Scholar]
- Lin K. T., Lee C. J. Immune response of neonates to pneumococcal polysaccharide-protein conjugate. Immunology. 1982 Jun;46(2):333–342. [PMC free article] [PubMed] [Google Scholar]
- Lu C. H., Hugh R., Lee C. J. Characterization of the binding of and the immune response to pneumococcal group 9 capsular polysaccharides. Mol Immunol. 1987 May;24(5):427–433. doi: 10.1016/0161-5890(87)90016-2. [DOI] [PubMed] [Google Scholar]
- Mellander L., Carlsson B., Hanson L. A. Secretory IgA and IgM antibodies to E. coli O and poliovirus type I antigens occur in amniotic fluid, meconium and saliva from newborns. A neonatal immune response without antigenic exposure: a result of anti-idiotypic induction? Clin Exp Immunol. 1986 Mar;63(3):555–561. [PMC free article] [PubMed] [Google Scholar]
- Musher D. M., Luchi M. J., Watson D. A., Hamilton R., Baughn R. E. Pneumococcal polysaccharide vaccine in young adults and older bronchitics: determination of IgG responses by ELISA and the effect of adsorption of serum with non-type-specific cell wall polysaccharide. J Infect Dis. 1990 Apr;161(4):728–735. doi: 10.1093/infdis/161.4.728. [DOI] [PubMed] [Google Scholar]
- Perry M. B., Daoust V., Carlo D. J. The specific capsular polysaccharide of Streptococcus pneumoniae type 9V. Can J Biochem. 1981 Jul;59(7):524–533. doi: 10.1139/o81-073. [DOI] [PubMed] [Google Scholar]
- Reth M., Kelsoe G., Rajewsky K. Idiotypic regulation by isologous monoclonal anti-idiotope antibodies. Nature. 1981 Mar 19;290(5803):257–259. doi: 10.1038/290257a0. [DOI] [PubMed] [Google Scholar]
- Robbins J. B., Austrian R., Lee C. J., Rastogi S. C., Schiffman G., Henrichsen J., Mäkelä P. H., Broome C. V., Facklam R. R., Tiesjema R. H. Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups. J Infect Dis. 1983 Dec;148(6):1136–1159. doi: 10.1093/infdis/148.6.1136. [DOI] [PubMed] [Google Scholar]
- Robbins J. B., Schneerson R. Polysaccharide-protein conjugates: a new generation of vaccines. J Infect Dis. 1990 May;161(5):821–832. doi: 10.1093/infdis/161.5.821. [DOI] [PubMed] [Google Scholar]
- Schiffman G., Douglas R. M., Bonner M. J., Robbins M., Austrian R. A radioimmunoassay for immunologic phenomena in pneumococcal disease and for the antibody response to pneumococcal vaccines. I. Method for the radioimmunoassay of anticapsular antibodies and comparison with other techniques. J Immunol Methods. 1980;33(2):133–144. doi: 10.1016/s0022-1759(80)80004-4. [DOI] [PubMed] [Google Scholar]
- Schneerson R., Barrera O., Sutton A., Robbins J. B. Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates. J Exp Med. 1980 Aug 1;152(2):361–376. doi: 10.1084/jem.152.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneerson R., Robbins J. B., Parke J. C., Jr, Bell C., Schlesselman J. J., Sutton A., Wang Z., Schiffman G., Karpas A., Shiloach J. Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates. Infect Immun. 1986 May;52(2):519–528. doi: 10.1128/iai.52.2.519-528.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shyamala G. N., Roberton D. M., Hosking C. S. Human-isotype-specific enzyme immunoassay for antibodies to pneumococcal polysaccharides. J Clin Microbiol. 1988 Aug;26(8):1575–1579. doi: 10.1128/jcm.26.8.1575-1579.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siber G. R., Ambrosino D. M., McIver J., Ervin T. J., Schiffman G., Sallan S., Grady G. F. Preparation of human hyperimmune globulin to Haemophilus influenzae b, Streptococcus pneumoniae, and Neisseria meningitidis. Infect Immun. 1984 Jul;45(1):248–254. doi: 10.1128/iai.45.1.248-254.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siber G. R., Priehs C., Madore D. V. Standardization of antibody assays for measuring the response to pneumococcal infection and immunization. Pediatr Infect Dis J. 1989 Jan;8(1 Suppl):S84–S91. [PubMed] [Google Scholar]
- Staros J. V., Wright R. W., Swingle D. M. Enhancement by N-hydroxysulfosuccinimide of water-soluble carbodiimide-mediated coupling reactions. Anal Biochem. 1986 Jul;156(1):220–222. doi: 10.1016/0003-2697(86)90176-4. [DOI] [PubMed] [Google Scholar]
- Stein K. E., Söderström T. Neonatal administration of idiotype or antiidiotype primes for protection against Escherichia coli K13 infection in mice. J Exp Med. 1984 Oct 1;160(4):1001–1011. doi: 10.1084/jem.160.4.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Verheul A. F., Versteeg A. A., De Reuver M. J., Jansze M., Snippe H. Modulation of the immune response to pneumococcal type 14 capsular polysaccharide-protein conjugates by the adjuvant Quil A depends on the properties of the conjugates. Infect Immun. 1989 Apr;57(4):1078–1083. doi: 10.1128/iai.57.4.1078-1083.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinberg G. A., Einhorn M. S., Lenoir A. A., Granoff P. D., Granoff D. M. Immunologic priming to capsular polysaccharide in infants immunized with Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine. J Pediatr. 1987 Jul;111(1):22–27. doi: 10.1016/s0022-3476(87)80336-0. [DOI] [PubMed] [Google Scholar]
