Frontiers of Medicine

, Volume 10, Issue 4, pp 490–498 | Cite as

Immunogenicity and protective immunity against otitis media caused by pneumococcus in mice of Hib conjugate vaccine with PsaA protein carrier

  • Zeyu Chen
  • Rong Guo
  • Jianghong Xu
  • Chuangjun Qiu
Research Article


This study evaluated the immunogenicity and protective immunity of a Hemophilus influenzae b (Hib) polysaccharide conjugate vaccine with the pneumococcal surface adhesin A (PsaA) protein carrier in young mice. The Hib polysaccharide was conjugated with the rPsaA protein carrier, which was produced using recombinant DNA technology. A total of 15 young mice aged 3 weeks to 5 weeks were immunized with the conjugate vaccine, and another 15 young mice of the same age were immunized with the licensed Hib-tetanus toxoid (TT) vaccine. Furthermore, the third group of 15 young mice was inoculated with phosphate buffer saline as control. The immunized mice were inoculated with pneumococcus in the middle ear. Results showed that IgG antibody responses against both the PsaA protein and Hib polysaccharide were observed in the Hib-PsaA group. However, no statistical difference was observed in the titer of IgG against the Hib polysaccharide between Hib-PsaA and Hib-TT groups. The elimination rate of pneumococcus and the inflammation of the middle ear showed the effectiveness of protective immunity against otitis media caused by pneumococcus. Our results suggest that the Hib polysaccharide can be successfully conjugated with rPsaA via amide condensation. This new Hib-PsaA conjugate vaccine can induce both anti-PsaA and anti-Hib immune responses in young mice and elicit effective protection against acute otitis media caused by pneumococcus.


conjugate vaccine pneumococcal surface adhesin A Hemophilus influenzaeimmunogenicity otitis media 


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  1. 1.
    Hasegawa J, Mori M, Showa S, Matsushima A, Ohnishi H, Tsugawa T, Yoto Y, Tsutsumi H. Pneumococcal vaccination reduced the risk of acute otitis media: cohort study. Pediatr Int 2015; 57(4): 582–585CrossRefPubMedGoogle Scholar
  2. 2.
    Intakorn P, Sonsuwan N, Noknu S, Moungthong G, Pirçon JY, Liu Y, Van Dyke MK, Hausdorff WP. Haemophilus influenzae type b as an important cause of culture-positive acute otitis media in young children in Thailand: a tympanocentesis-based, multi-center, crosssectional study. BMC Pediatr 2014; 14(1): 157CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kim KH, Lee H, Chung EH, Kang JH, Kim JH, Kim JS, Lee HJ, Oh SH, Park EA, Park SE. Immunogenicity and safety of two different Haemophilus influenzae type b conjugate vaccines in Korean infants. J Korean Med Sci 2008; 23(6): 929–936CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Yatsyshina S, Mayanskiy N, Shipulina O, Kulichenko T, Alyabieva N, Katosova L, Lazareva A, Skachkova T, Elkina M, Matosova S, Shipulin G. Detection of respiratory pathogens in pediatric acute otitis media by PCR and comparison of findings in the middle ear and nasopharynx. Diagn Microbiol Infect Dis 2016; 85(1): 125–130CrossRefPubMedGoogle Scholar
  5. 5.
    Pumarola F, Marès J, Losada I, Minguella I, Moraga F, Tarragó D, Aguilera U, Casanovas JM, Gadea G, Trías E, Cenoz S, Sistiaga A, García-Corbeira P, Pirçon JY, Marano C, Hausdorff WP. Microbiology of bacteria causing recurrent acute otitis media (AOM) and AOM treatment failure in young children in Spain: shifting pathogens in the post-pneumococcal conjugate vaccination era. Int J Pediatr Otorhinolaryngol 2013; 77(8): 1231–1236CrossRefPubMedGoogle Scholar
  6. 6.
    Dagan R, Eskola J, Leclerc C, Leroy O. Reduced response to multiple vaccines sharing common protein epitopes that are administered simultaneously to infants. Infect Immun 1998; 66(5): 2093–2098PubMedPubMedCentralGoogle Scholar
  7. 7.
    Insel RA. Potential alterations in immunogenicity by combining or simultaneously administering vaccine components. Ann N Y Acad Sci 1995; 754(1 Combined Vacc): 35–47CrossRefPubMedGoogle Scholar
  8. 8.
    Sabirov A, Kodama S, Hirano T, Suzuki M, Mogi G. Intranasal immunization enhances clearance of nontypeable Haemophilus influenzae and reduces stimulation of tumor necrosis factor alpha production in the murine model of otitis media. Infect Immun 2001; 69(5): 2964–2971CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Sipilä M, Pukander J, Karma P. Incidence of acute otitis media up to the age of 1 1/2 years in urban infants. Acta Otolaryngol 1987; 104 (1-2): 138–145CrossRefPubMedGoogle Scholar
  10. 10.
    Faden H, Duffy L, Boeve M. Otitis media: back to basics. Pediatr Infect Dis J 1998; 17(12): 1105–1112, quiz 1112–1113CrossRefPubMedGoogle Scholar
  11. 11.
    Qureishi A, Lee Y, Belfield K, Birchall JP, Daniel M. Update on otitis media —prevention and treatment. Infect Drug Resist 2014; 7 (1): 15–24PubMedPubMedCentralGoogle Scholar
  12. 12.
    Dowell SF, Butler JC, Giebink GS, Jacobs MR, Jernigan D, Musher DM, Rakowsky A, Schwartz B. Acute otitis media: management and surveillance in an era of pneumococcal resistance—a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr Infect Dis J 1999; 18(1): 1–9CrossRefPubMedGoogle Scholar
  13. 13.
    O’Brien KL, Dagan R, Mäkelä PH. Nasopharyngeal carriage. In: Siber GR, Klugman KP, Mäkelä PH. Pneumococcal Vaccines: the Impact of Conjugate Vaccine. Washington, DC: ASM Press, 2008:279–300Google Scholar
  14. 14.
    Henrichsen J. Six newly recognized types of Streptococcus pneumoniae. J Clin Microbiol 1995; 33(10): 2759–2762PubMedPubMedCentralGoogle Scholar
  15. 15.
    Dhooge IJ, van Kempen MJ, Sanders LA, Rijkers GT. Deficient IgA and IgG2 anti-pneumococcal antibody levels and response to vaccination in otitis prone children. Int J Pediatr Otorhinolaryngol 2002; 64(2): 133–141CrossRefPubMedGoogle Scholar
  16. 16.
    Sniadack DH, Schwartz B, Lipman H, Bogaerts J, Butler JC, Dagan R, Echaniz-Aviles G, Lloyd-Evans N, Fenoll A, Girgis NI, Henrichsen J, Klugman K, Lehmann D, Takala AK, Vandepitte J, Gove S, Breiman RF. Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children—implications for vaccine strategies. Pediatr Infect Dis J 1995; 14(6): 503–510CrossRefPubMedGoogle Scholar
  17. 17.
    Briles DE, Hollingshead SK, Crain MJ, Ren B, Mirza S, Watt J, Johnston J. Pneumococcal proteins that may constitute the next generation vaccine for pneumococcal disease. Int Congr Ser 2003; 1257: 27–31CrossRefGoogle Scholar
  18. 18.
    Briles DE, Hollingshead S, Brooks-Walter A, Nabors GS, Ferguson L, Schilling M, Gravenstein S, Braun P, King J, Swift A. The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection. Vaccine 2000; 18(16): 1707–1711CrossRefPubMedGoogle Scholar
  19. 19.
    Bogaert D, Hermans PW, Adrian PV, Rümke HC, de Groot R. Pneumococcal vaccines: an update on current strategies. Vaccine 2004; 22(17-18): 2209–2220CrossRefPubMedGoogle Scholar
  20. 20.
    Briles DE, Hollingshead SK, Nabors GS, Paton JC, Brooks-Walter A. The potential for using protein vaccines to protect against otitis media caused by Streptococcus pneumoniae. Vaccine 2000; 19 (Suppl 1): S87–S95CrossRefPubMedGoogle Scholar
  21. 21.
    Butler JC, Breiman RF, Lipman HB, Hofmann J, Facklam RR. Serotype distribution of Streptococcus pneumoniae infections among preschool children in the United States, 1978–1994: implications for development of a conjugate vaccine. J Infect Dis 1995; 171(4): 885–889CrossRefPubMedGoogle Scholar
  22. 22.
    Mayanskiy N, Alyabieva N, Ponomarenko O, Pakhomov A, Kulichenko T, Ivanenko A, Lazareva M, Lazareva A, Katosova L, Namazova-Baranova L, Baranov A. Bacterial etiology of acute otitis media and characterization of pneumococcal serotypes and genotypes among children in Moscow, Russia. Pediatr Infect Dis J 2015; 34(3): 255–260CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Zeyu Chen
    • 1
    • 2
  • Rong Guo
    • 3
  • Jianghong Xu
    • 1
    • 2
  • Chuangjun Qiu
    • 4
  1. 1.Department of Otorhinolaryngology, Eye & ENT HospitalFudan UniversityShanghaiChina
  2. 2.Shanghai Clinical Medical Center of Hearing MedicineShanghaiChina
  3. 3.The Laboratory of Bacterial VaccineWuhan Institute of Biological ProductsWuhanChina
  4. 4.Dingtai-Haigui Biotechnology Co. Ltd.Gu’anChina

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