Immunogenicity and safety of a trivalent inactivated influenza vaccine

Eddy Fadlyana; Kusnandi Rusmil; Novilia Sjafri Bachtiar; Rachmat Gunadi; Hadyana Sukandar

doi:10.14238/pi51.1.2011.22-8

Eddy Fadlyana Department of Child Health, Universitas Padjadjaran Medical School/Dr. Hasan Sadikin Hospital, Bandung, West Java
Kusnandi Rusmil Department of Child Health, Universitas Padjadjaran Medical School/Dr. Hasan Sadikin Hospital, Bandung, West Java
Novilia Sjafri Bachtiar Bio Farma Pharmaceuthical Company, Bandung, West Java
Rachmat Gunadi Department of Internal Medicine, Universitas Padjadjaran Medical School/Dr. Hasan Sadikin Hospital, Bandung, West Java
Hadyana Sukandar Department of Epidemiology & Biostatistics, Universitas Padjadjaran Medical School/Dr. Hasan Sadikin Hospital, Bandung, West Java

DOI: https://doi.org/10.14238/pi51.1.2011.22-8

Keywords: adolescents, adult, inactivated influenza vaccine, immunogenicity, safety

Abstract

Background Trivalent inactivated influenza vaccines (TIV) containing antigens of two influenza A strains, A(H1N1) and A(H3N2), and one influenza B strain, are the standard {onnulation for influenza prevention. The vaccines must be updated annually to provide optimal protection against the predicted prevalent strains for the next influenza season.

Objective To assess the immunogenidty and safety of the inactivated influenza vaccine (FlubioÂ®) in adolescents and adults, 28 days after a single dose.

Methods In this experimental, randomized, single-blind, bridging study, we included 60 healthy adolescents and adults. A single, 0.5 mL dose was administered intramuscularly in the deltoid muscle of the left ann. Blood samples were obtained before and 28 days after immunization. Standardized hemagglutination inhibition (HI) test was used to assess antibody response to influenza antigens.

Results From January to February 2010, a total of 60 adolescents and adults enrolled in the study, but two participants did not provide the required blood samples. One hundred percent of the subjects had an anti-influenza titer â‰¥ 1:40 HI units to all three strains, A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2), and B/Brisbane/60/2008 (P=1.000) after immunization. The Geometric Mean Titers (GMT) after immunization increased

for all strains: A/Brisbane, 76.4 to 992.7, A/Uruguay, 27.6 to 432.1, and B/Brisbane, 19.9 to 312.7. Twenty eight days after immunization, we found a 4 times increase in antibody titers in 75.8% of the subjects for A/Brisbane, 84.5% for A/Uruguay, and 77.6% for B/Brisbane. We also observed that 100% of seronegative subjects converted to seropositive for all 3 strains. All vaccines were well-tolerated. There were no serious adverse events reported during the study.

Conclusion In adolescents and adults, the FlubioÂ® vaccine was immunogenic and safe.

References

1. Schanzer DL, Langley JM, Tam TW. Hospitalization attributable to influenza and other viral respiratory illnesses in Canadian children. Pediatr Infect Dis J. 2006;25:795-800.
2. Thompson Ww, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, et al. Influenza-associated hospitalizations in the United States. JAMA. 2004:292:1333-40.
3. Thompson ww, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated 'With influenza and respiratory syncytial virus in the United States. JAMA. 2003:289:179-86.
4. World Health Organization. WHO factsheet 211: Influenza. 2009 [cited 2009 Oct 15]. Available from: http://who.int/ mediacentre/factsheets/2009/fs211/ en/print. html
5. Yuwono D, P utranto RH, Sehatman, Subangkitl, Nut K, Susilowati et al. Epidemiological study of influenza in Jakarta and surrounding areas. Bul Penel Kesehatan. 2008;36:71-82.
6. Balkhy HH, Memish ZA, Bafaqeer S, Almuneef MA. Influenza a common viral infection among Hajj pilgrims: time for routine surveillance and vaccination. J Travel Med. 2004;11:82-6.
7. World Health Organization. WHO global influenza surveillance network. [update 2011, cited 2011 Jan 05]. Available from: http://www.who.int/ csr/ disease/influenza/ surveillance/en/index.html. S. World Health Organization. Recommended composition of influenza virus vaccines in 2009. Available from: \VWW.who. int/entity/csr/disease/influenza/200S09Recommen dation. pdf.
9. Food and Drug Administration, US Department of Health and Human Services. Guidance for Industry: Choice of control group and related issues in clinical trials, May 2001.
10. Food and Drug Administration, US Department of Health and Human Services. Guidance for Industry: Ethnic factors in the acceptability of foreign clinical data, Sep 2006.
11. Food and Drug Administration, US Department of Health and Human Services. Guidance for Industry: Clinical safety data management, definitions and standards for expedited reporting, Mar 1995.
12. Indonesian Food and Drugs Association. Cara uji klinik yang baik, 2000.
13. Hahon N, Booth JA, Eckert HL. Further studies on the anti immunoglobulin G hemagglutination - inhibition test for influema. Appl Microbiol. 1972;23:485-9.
14. Food and Drug Administration, US Department of Health and Human Services. Guidance for industry: Toxicity grading scale for healthy adult and adolescent volunteers' enrolled in preventive vaccine trials, Apr 2005.
15. Wright P, Webster R. Orthomyxoviruses. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, et al, editors. Fields virology. 4th Ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p.1534-79.
16. Food and Drug Administration, US Department of Health and Human Services. Guidences for industry: Clinical data needed to support the licensure of seasonal inactivated influenza vaccines, May 2007.
17. Verthelyi D. Sex hormones as immunomodulators in health and disease. Int Immunophannacol. 2001;1:9S3-93.
18. Stimson WHo Oestrogen and human T lymphocytes: presence of specific receptors in the T-suppressor/cytotoxic subset. Scand J Immunol. 1998;28:345-50.
19. Benten WPM, Stephan C, Wunderlich F. B cells express intracellular but not surface receptors for testosterone and estradiol. Steroids. 2002;67:647-54.
20. Rusmil K, Fadlyana E, Gunadi R , Dhamayanti M, Boedisetianto E, Bachtiar NS. Protectivity and safety of Influenza HA (Bio Fanna) vaccine in adolescents and adults (Bridging Study). Proceedings of the 13 th Asian Pacific Congress of Pediatrics, Shanghai, China; 2009 October 14-18.
21. Jackson LA, Gaglani MJ, Keyserling HL, Balser J, Bouveret N, Fries L and Treanor J]. Safety, efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized, placeboô€©controlled trial over two influenza seasons. BMC Infect Dis. 2010;10:71.
22. Govaert ME,D inant GJ,A retz K,M asurel N,S prenger MJW, Knottnerus JA. Adverse reactions to influenza vaccine in elderly people: randomized double blind placebo controlled trial. BMJ. 1993;307:988-90.
23. Margolis KL, Nichol KL, Poland GA, Pluhar RE. Frequency of adverse reactions to influenza vaccine in the elderly: a randomhed, placebo-controlled trial. JAMA. 1990;264:1139- 41.
24. Nichol KL, Margolis KL, Lind A, Murdoch M, McFadden R, Hauge M, et al. Sideô€©effects associated v.ith influenza vaccination in healthy working adults: a randomized, placebo-controlled trial. Arch Internal Med. 1996;156:1546-50.
25. Supplementary information on vaccine safety part 2 : Background rates of adverse events follov.ing immunization. Geneva: World Health Organization, 2000.
26. Barry DW, Mayner RE, Hochstein HD, Dunlap RC, Rastogi SC,H annah JE,e t al. Comparative trial of influenza vaccines. II. Adverse reactions in children and adults. Am J Epidemiol. 1976;104:47-59.