Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 May;65(5):1710–1715. doi: 10.1128/iai.65.5.1710-1715.1997

MF59 adjuvant enhances antibody responses of infant baboons immunized with Haemophilus influenzae type b and Neisseria meningitidis group C oligosaccharide-CRM197 conjugate vaccine.

D M Granoff 1, Y E McHugh 1, H V Raff 1, A S Mokatrin 1, G A Van Nest 1
PMCID: PMC175202  PMID: 9125551

Abstract

The ability of the adjuvant MF59 to enhance the immunogenicity of polysaccharide-protein conjugate vaccines was investigated in infant baboons. MF59 consists of stable droplets (<250 nm) of the metabolizable oil squalene and two surfactants, polyoxyethylene sorbitan monooleate and sorbitan trioleate, in an oil-in-water emulsion. In humans, MF59 is well tolerated and enhances the immunogenicity of recombinant protein subunit or particle vaccines. Its effect on the immunogenicity of polysaccharide-protein conjugate vaccines is unknown. Baboons 1 to 4 months of age were immunized intramuscularly with Neisseria meningitidis group C and Haemophilus influenzae type b (Hib) oligosaccharide-CRM197 conjugate vaccines. The lyophilized vaccines were reconstituted with phosphate-buffered saline (PBS), Al(OH)3 (alum), or MF59. Groups of five animals each were given three injections of the respective formulations, with one injection every 4 weeks. Four weeks after each immunization, the MF59 group had up to 7-fold-higher geometric mean anticapsular-antibody titers than the alum group and 5- to 10-fold-higher N. meningitidis group C bactericidal-antibody titers. Twenty-one weeks after the third immunization, the MF59 group still showed 5- to 10-fold-higher anticapsular-antibody titers. The antibody responses of the animals given the vaccines reconstituted with PBS were low at all times measured. Both the MF59 and alum groups, but not the PBS group, showed booster antibody responses to unconjugated Hib and N. meningitidis group C polysaccharides, results consistent with induction of memory B cells. Thus, MF59 may be useful for accelerating and augmenting immunity to polysaccharide-protein conjugate vaccines in infants.

Full Text

The Full Text of this article is available as a PDF (197.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams W. G., Deaver K. A., Cochi S. L., Plikaytis B. D., Zell E. R., Broome C. V., Wenger J. D. Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era. JAMA. 1993 Jan 13;269(2):221–226. [PubMed] [Google Scholar]
  2. Amir J., Scott M. G., Nahm M. H., Granoff D. M. Bactericidal and opsonic activity of IgG1 and IgG2 anticapsular antibodies to Haemophilus influenzae type b. J Infect Dis. 1990 Jul;162(1):163–171. doi: 10.1093/infdis/162.1.163. [DOI] [PubMed] [Google Scholar]
  3. Anderson P. Antibody responses to Haemophilus influenzae type b and diphtheria toxin induced by conjugates of oligosaccharides of the type b capsule with the nontoxic protein CRM197. Infect Immun. 1983 Jan;39(1):233–238. doi: 10.1128/iai.39.1.233-238.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Artenstein M. S., Gold R., Zimmerly J. G., Wyle F. A., Schneider H., Harkins C. Prevention of meningococcal disease by group C polysaccharide vaccine. N Engl J Med. 1970 Feb 19;282(8):417–420. doi: 10.1056/NEJM197002192820803. [DOI] [PubMed] [Google Scholar]
  5. Centers for Disease Control and Prevention (CDC) Progress toward elimination of Haemophilus influenzae type b disease among infants and children--United States, 1987-1995. MMWR Morb Mortal Wkly Rep. 1996 Oct 25;45(42):901–906. [PubMed] [Google Scholar]
  6. Costantino P., Viti S., Podda A., Velmonte M. A., Nencioni L., Rappuoli R. Development and phase 1 clinical testing of a conjugate vaccine against meningococcus A and C. Vaccine. 1992;10(10):691–698. doi: 10.1016/0264-410x(92)90091-w. [DOI] [PubMed] [Google Scholar]
  7. Granoff D. M., Holmes S. J., Belshe R. B., Osterholm M. T., McHugh J. E., Anderson E. L. Effect of carrier protein priming on antibody responses to Haemophilus influenzae type b conjugate vaccines in infants. JAMA. 1994 Oct 12;272(14):1116–1121. [PubMed] [Google Scholar]
  8. Granoff D. M., Holmes S. J., Osterholm M. T., McHugh J. E., Lucas A. H., Anderson E. L., Belshe R. B., Jacobs J. L., Medley F., Murphy T. V. Induction of immunologic memory in infants primed with Haemophilus influenzae type b conjugate vaccines. J Infect Dis. 1993 Sep;168(3):663–671. doi: 10.1093/infdis/168.3.663. [DOI] [PubMed] [Google Scholar]
  9. Granoff D. M., Kelsey S. K., Bijlmer H. A., Van Alphen L., Dankert J., Mandrell R. E., Azmi F. H., Scholten R. J. Antibody responses to the capsular polysaccharide of Neisseria meningitidis serogroup B in patients with meningococcal disease. Clin Diagn Lab Immunol. 1995 Sep;2(5):574–582. doi: 10.1128/cdli.2.5.574-582.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Granoff D. M., Rathore M. H., Holmes S. J., Granoff P. D., Lucas A. H. Effect of immunity to the carrier protein on antibody responses to Haemophilus influenzae type b conjugate vaccines. Vaccine. 1993;11 (Suppl 1):S46–S51. doi: 10.1016/0264-410x(93)90160-y. [DOI] [PubMed] [Google Scholar]
  11. Gupta R. K., Anderson R., Cecchini D., Rost B., Griffin P., Jr, Benscoter K., Xu J., Montanez-Ortiz L., Siber G. R. Development of a guinea-pig model for potency/immunogenicity evaluation of diphtheria, tetanus acellular pertussis (DTaP) and Haemophilus influenzae type b polysaccharide conjugate vaccines. Dev Biol Stand. 1996;86:283–296. [PubMed] [Google Scholar]
  12. Kahn J. O., Sinangil F., Baenziger J., Murcar N., Wynne D., Coleman R. L., Steimer K. S., Dekker C. L., Chernoff D. Clinical and immunologic responses to human immunodeficiency virus (HIV) type 1SF2 gp120 subunit vaccine combined with MF59 adjuvant with or without muramyl tripeptide dipalmitoyl phosphatidylethanolamine in non-HIV-infected human volunteers. J Infect Dis. 1994 Nov;170(5):1288–1291. doi: 10.1093/infdis/170.5.1288. [DOI] [PubMed] [Google Scholar]
  13. Langenberg A. G., Burke R. L., Adair S. F., Sekulovich R., Tigges M., Dekker C. L., Corey L. A recombinant glycoprotein vaccine for herpes simplex virus type 2: safety and immunogenicity [corrected]. Ann Intern Med. 1995 Jun 15;122(12):889–898. doi: 10.7326/0003-4819-122-12-199506150-00001. [DOI] [PubMed] [Google Scholar]
  14. Leach A., Twumasi P. A., Kumah S., Banya W. S., Jaffar S., Forrest B. D., Granoff D. M., LiButti D. E., Carlone G. M., Pais L. B. Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide-protein conjugate vaccine. J Infect Dis. 1997 Jan;175(1):200–204. doi: 10.1093/infdis/175.1.200. [DOI] [PubMed] [Google Scholar]
  15. Lieberman J. M., Chiu S. S., Wong V. K., Partidge S., Chang S. J., Chiu C. Y., Gheesling L. L., Carlone G. M., Ward J. I. Safety and immunogenicity of a serogroups A/C Neisseria meningitidis oligosaccharide-protein conjugate vaccine in young children. A randomized controlled trial. JAMA. 1996 May 15;275(19):1499–1503. [PubMed] [Google Scholar]
  16. Mandrell R. E., Azmi F. H., Granoff D. M. Complement-mediated bactericidal activity of human antibodies to poly alpha 2-->8 N-acetylneuraminic acid, the capsular polysaccharide of Neisseria meningitidis serogroup B. J Infect Dis. 1995 Nov;172(5):1279–1289. doi: 10.1093/infdis/172.5.1279. [DOI] [PubMed] [Google Scholar]
  17. Milagres L. G., Ramos S. R., Sacchi C. T., Melles C. E., Vieira V. S., Sato H., Brito G. S., Moraes J. C., Frasch C. E. Immune response of Brazilian children to a Neisseria meningitidis serogroup B outer membrane protein vaccine: comparison with efficacy. Infect Immun. 1994 Oct;62(10):4419–4424. doi: 10.1128/iai.62.10.4419-4424.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Murphy T. V., White K. E., Pastor P., Gabriel L., Medley F., Granoff D. M., Osterholm M. T. Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination. JAMA. 1993 Jan 13;269(2):246–248. [PubMed] [Google Scholar]
  19. Ott G., Barchfeld G. L., Chernoff D., Radhakrishnan R., van Hoogevest P., Van Nest G. MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol. 1995;6:277–296. doi: 10.1007/978-1-4615-1823-5_10. [DOI] [PubMed] [Google Scholar]
  20. Peeters C. C., Tenbergen-Meekes A. M., Poolman J. T., Beurret M., Zegers B. J., Rijkers G. T. Effect of carrier priming on immunogenicity of saccharide-protein conjugate vaccines. Infect Immun. 1991 Oct;59(10):3504–3510. doi: 10.1128/iai.59.10.3504-3510.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Podda A., Nencioni L., De Magistris M. T., Di Tommaso A., Bossù P., Nuti S., Pileri P., Peppoloni S., Bugnoli M., Ruggiero P. Metabolic, humoral, and cellular responses in adult volunteers immunized with the genetically inactivated pertussis toxin mutant PT-9K/129G. J Exp Med. 1990 Sep 1;172(3):861–868. doi: 10.1084/jem.172.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Robbins J. B., Parke J. C., Jr, Schneerson R., Whisnant J. K. Quantitative measurement of "natural" and immunization-induced Haemophilus influenzae type b capsular polysaccharide antibodies. Pediatr Res. 1973 Mar;7(3):103–110. doi: 10.1203/00006450-197303000-00001. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Schneerson R., Robbins J. B., Chu C., Sutton A., Vann W., Vickers J. C., London W. T., Curfman B., Hardegree M. C., Shiloach J. Serum antibody responses of juvenile and infant rhesus monkeys injected with Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-protein conjugates. Infect Immun. 1984 Sep;45(3):582–591. doi: 10.1128/iai.45.3.582-591.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schutze M. P., Deriaud E., Przewlocki G., LeClerc C. Carrier-induced epitopic suppression is initiated through clonal dominance. J Immunol. 1989 Apr 15;142(8):2635–2640. [PubMed] [Google Scholar]
  26. Siber G. R., Anderson R., Habafy M., Gupta R. K. Development of a guinea pig model to assess immunogenicity of Haemophilus influenzae type b capsular polysaccharide conjugate vaccines. Vaccine. 1995 Apr;13(6):525–531. doi: 10.1016/0264-410x(94)00042-l. [DOI] [PubMed] [Google Scholar]
  27. Siber G. R. Pneumococcal disease: prospects for a new generation of vaccines. Science. 1994 Sep 2;265(5177):1385–1387. doi: 10.1126/science.8073278. [DOI] [PubMed] [Google Scholar]
  28. Twumasi P. A., Jr, Kumah S., Leach A., O'Dempsey T. J., Ceesay S. J., Todd J., Broome C. V., Carlone G. M., Pais L. B., Holder P. K. A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants. J Infect Dis. 1995 Mar;171(3):632–638. doi: 10.1093/infdis/171.3.632. [DOI] [PubMed] [Google Scholar]
  29. Vella P. P., Ellis R. W. Immunogenicity of Haemophilus influenzae type b conjugate vaccines in infant rhesus monkeys. Pediatr Res. 1991 Jan;29(1):10–13. doi: 10.1203/00006450-199101000-00003. [DOI] [PubMed] [Google Scholar]
  30. Vella P. P., Staub J. M., Armstrong J., Dolan K. T., Rusk C. M., Szymanski S., Greer W. E., Marburg S., Kniskern P. J., Schofield T. L. Immunogenicity of a new Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB). Pediatrics. 1990 Apr;85(4 Pt 2):668–675. [PubMed] [Google Scholar]
  31. Wang J. B., Adler S. P., Hempfling S., Burke R. L., Duliège A. M., Starr S. E., Plotkin S. A. Mucosal antibodies to human cytomegalovirus glycoprotein B occur following both natural infection and immunization with human cytomegalovirus vaccines. J Infect Dis. 1996 Aug;174(2):387–392. doi: 10.1093/infdis/174.2.387. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES