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ISSN 1027-2852 (Electronic)
ISSN 0864-4551 (Print)

2013, Number 2

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Biotecnol Apl 2013; 30 (2)

Preclinical safety of the Quimi-Hib® vaccine adjuvanted with aluminum phosphate during product development

Bacardí D, Cosme K, Aldana L, Merino N, Suárez J, Mosqueda O, Urquiza D, Romero J, Madrigal R, Amaya R, Hernández L

Language: Spanish
References: 22
Page: 111-124
PDF size: 267.21 Kb.


ABSTRACT

Haemophilus influenzae type b (Hib) is a Gram-negative bacterium causing diseases such as meningitis, pneumonia, epiglottis, cellulitis, septicemia and arthritis, among others. Hib-caused meningitis / Hib meningitis is a very serious disease with a death rate of more than 50 % throughout the world; therefore obtaining a vaccine against this bacterium is a goal of the highest priority. The present report presents the results of preclinical safety testing of the Quimi-Hib® vaccine (synthetic Hib antigen conjugated to tetanus toxoid) adjuvanted with aluminum phosphate. The battery of toxicological tests included acute toxicity (15 days), local tolerance (15 days) and repeated-dose toxicity (30 days), all of them evaluating the therapeutic dose of the vaccine as part of the studied experimental treatments. Three vaccine dose levels and a placebo (excipients plus adjuvant) were examined, administering the vaccine intramuscularly to Sprague Dawley rats of both sexes. After examining the data obtained from the administration of this wide range of doses to Sprague Dawley rats, it was concluded that the synthetic conjugate vaccine Quimi-Hib® adjuvanted in aluminum phosphate is not toxic and does not cause systemic adverse effects. No macroscopic alterations were observed in the studied organs, and the evaluation of the inoculation site only detected indurations caused by macrophage granulomas, resulting from the mechanism of action of the adjuvant included in the formulation.


REFERENCES

  1. Robbins JB, Schneerson R. Haemophilus influenzae type b: the search for a vaccine. Pediatr Infect Dis J. 1987;6(8):791-4.

  2. Ahmed N, Gottschalk S. How to design effective vaccines: lessons from an old success story. Expert Rev Vaccines. 2009; 8(5):543-6.

  3. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Effi cacy and effectiveness of infl uenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012; 12(1):36-44.

  4. Fitzwater SP, Watt JP, Levine OS, Santosham M. Haemophilus influenzae type b conjugate vaccines: considerations for vaccination schedules and implications for developing countries. Hum Vaccines. 2010;6(10):810-8.

  5. Peltola H. Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev. 2000;13(2):302-17.

  6. Plotkin SA. Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010;17(7):1055-65.

  7. Verez-Bencomo V, Fernandez-Santana V, Hardy E, Toledo ME, Rodriguez MC, Heynngnezz L, et al. A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b. Science. 2004; 305(5683):522-5.

  8. European Medicines Agency. CPMP/ SWP/465/95. Note for guidance on preclinical pharmacological and toxicological testing of vaccines (CPMP adopted Dec 97). London: EMA; 1997 (cited 2012 Apr 16). Available from: http://www.ema.europa. eu/docs/en_GB/document_library/Scientifi c_guideline/2009/10/WC500004004. pdf

  9. European Medicines Agency. CPMP/ SWP/1042/99. Note for guidance on repeated dose toxicity (CPMP adopted July 2000). London: EMA cited 2012 Apr 16). Available from: http://www.ema.europa. eu/docs/en_GB/document_library/Scientifi c_guideline/2009/09/WC500003102. pdf

  10. European Medicines Agency. CPMP/ ICH/286/95. Note for guidance on Nonclinical safety studies for the conduct of Human clinical trials for pharmaceuticals. ICH M3 (R2). 2008. Available from: http://www. ema.europa.eu/docs/en_GB/document_ library/Scientific_guideline/2009/09/ WC500002941.pdf

  11. Diehl KH, Hull R, Morton D, Pfi ster R, Rabemampianina Y, Smith D, et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol. 2001;21(1):15-23.

  12. Cosme K. Programa para el Uso de Animales de Experimentación del Centro de Ingeniería Genética y Biotecnología. Edición 01;1998.

  13. Van Zutphen LFM, Balls M . Animal Alternatives, Welfare and Ethics. Developments in Animal and Veterinary Sciences. Amsterdam: Elsevier Science Ltd.; 1997.

  14. Olfert ED, Cross BM, Mc William A. Guide to the care and use of experimental animals. 2nd ed. Ontario: Canadian Council on Animal Care; 1998.

  15. Harkness JE, Wagner JE. The Biology and Medicine of Rabbits and Rodents. 4th ed. Philadelphia, PA: Lea and Febiger; 1995.

  16. Lindblad EB. Aluminium adjuvants-in retrospect and prospect. Vaccine. 2004; 22(27-28):3658-68.

  17. Gupta RK. Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev. 1998;32(3):155-72.

  18. Harandi AM, Medaglini D, Shattock RJ. Vaccine adjuvants: a priority for vaccine research. Vaccine. 2010;28(12):2363-6.

  19. Chong H, Brady K, Metze D, Calonje E. Persistent nodules at injection sites (aluminium granuloma) - clinicopathological study of 14 cases with a diverse range of histological reaction patterns. Histopathology. 2006;48(2):182-8.

  20. Bordet AL, Michenet P, Cohen C, Arbion F, Ekindi N, Bonneau C, et al. Granulome post-vaccinal lié à l’hydroxyde d’aluminium. Ann Pathol. 2001;21(2): 149-52.

  21. Makwana N, Riordan FA. Bacterial meningitis: the impact of vaccination. CNS Drugs. 2007;21(5):355-66.

  22. Goto N, Kato H, Maeyama J, Shibano M, Saito T, Yamaguchi J, et al. Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties. Vaccine. 1997;15(12-13):1364-71.




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