Immunogenicity and Safety of Inactivated Influenza Vaccine in Healthy Korean Children and Adolescent

Soohyun Ri; Mi Jeong Kim; Yun-Kyung Kim

doi:10.14776/piv.2018.25.1.35

Journal List > Pediatr Infect Vaccine > v.25(1) > 1098702

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Ri, Kim, and Kim: Immunogenicity and Safety of Inactivated Influenza Vaccine in Healthy Korean Children and Adolescent

Original Article

Pediatr Infect Vaccine 2018;25(1):35-44.

Published online: 20 January 2018

DOI: https://doi.org/10.14776/piv.2018.25.1.35

Immunogenicity and Safety of Inactivated Influenza Vaccine in Healthy Korean Children and Adolescent

Soohyun Ri¹, Mi Jeong Kim², Yun-Kyung Kim^1,

¹Department of Pediatrics, Korea University Ansan Hospital, Korea University College of Medicine, Ansan

²Department of Pediatrics, Gyeonggi Provincial Medical Center Icheon Hospital, Icheon, the Republic of Korea

책임저자: Yun-Kyung Kim Department of Pediatrics, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea Tel: +82-31-412-4844, Fax: +82-31-405-8591 E-mail: byelhana@korea.ac.kr

Received 15 September 2017 Revised 16 October 2017 Accepted 18 October 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

This study aimed to evaluate the immunogenicity and safety of a trivalent inactivated influenza vaccine (TIV) among healthy Korean children and adolescents.

Methods

From October to December 2008, 65 healthy patients aged 6 months to 18 years who visited Korea University Ansan Hospital for influenza vaccination were enrolled in this study. We measured the hemagglutinin inhibition antibody titers at baseline and 30 days after vaccinating enrollees with split influenza vaccine and calculated the seroprotection rates, geometric mean titers, and seroconversion rates. Local and systemic adverse events were assessed after vaccination.

Results

The seroprotection rates against all three viral strains (A/H1N1, A/H3N2, B) were 87.7%, 89.2%, and 89.2% (≥70%), respectively; seroconversion rates were 44.6%, 73.8%, and 63.1% (≥40%), respectively; and seroconversion factors were 4.5, 8.4, and 10.5 (>2.5), respectively. The TIV immunogenicity was acceptable according to the CPMP (Committee for Proprietary Medicinal Products) criteria. Although 48 patients (73.8%) reported one or more adverse events, no severe adverse events such as anaphylaxis and convulsion were observed. Forty-two patients (64.6%) reported a local skin reaction, including redness (29.2%), pain (43.1%), or swelling (41.5%) of the injected site, and 26 (40.0%) reported a systemic reaction: fatigue (23.1%), myalgia (20.0%), headache (10.8%), arthralgia (10.8%), chills (9.2%), or fever (7.7%).

Conclusions

This study shows that the immunogenicity of the TIV vaccine is acceptable. As there were no serious adverse events aside from local reactions and mild systemic reactions, this vaccine can be safely used among healthy Korean children and adolescents.

Keywords: Influenza vaccines, Immunogenicity, vaccine, Safety

References

1. 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.

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. Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. 2009; 58(RR-8):1–52.

4. Cheong HJ, Song JY, Park JW, Yeon JE, Byun KS, Lee CH, et al. Humoral and cellular immune responses to influenza vaccine in patients with advanced cirrhosis. Vaccine. 2006; 24:2417–22.

5. Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008; 57(RR-7):1–60.

6. Organization for Economic Cooperation and Development (OECD). 2015 Influenza vaccination rates [Internet]. Paris: OECD;c2018. [cited 2018 Mar 17]. Available from:. https://data.oecd.org.

7. Korean Statistical Information Service. 2015 Influenza vaccination rate for children and adolescents [Internet]. Daejeon: Statistics Korea;2015. [cited 2018 Mar 17]. Available from:. http://kosis.kr.

8. Kim YK, Eun BW, Lee TJ, Lee J, Kim KH, Kim DH, et al. Immunogenicity and safety of a cell culture-derived inactivated quadrivalent influenza vaccine (NBP607-QIV) in South Korean children and adolescents: a randomized, double-blind, multicenter, phase 3 clinical trial. Open Forum Infect Dis. 2016; 3(Suppl 1):S201.

9. Cintra OA, Rey LC. Safety, immunogenicity and efficacy of influenza vaccine in children. J Pediatr (Rio J). 2006; 82(3 Suppl):S83–90.

10. Wright PF. The use of inactivated influenza vaccine in children. Semin Pediatr Infect Dis. 2006; 17:200–5.

11. Han SB, Rhim JW, Shin HJ, Lee SY, Kim HH, Kim JH, et al. Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial. Hum Vaccin Immunother. 2015; 11:1094–102.

12. Committee for Medicinal Products for Human Use. Guideline on dossier structure and content for pandemic influenza vaccine marketing authorisation application [Internet]. London: European Medicines Agency;2008. [cited 2018 Mar 17]. Available from:. http://www.ema. europa.eu.

13. Committee for Proprietary Medicinal Products. Note for guidance on harmonisation of requirements for influenza vaccines [Internet]. London: European Agency for the Evaluation of Medicinal Products;1997. [cited 2018 Mar 17]. Available from:. http://www.ema.europa.eu.

14. Walter EB, Rajagopal S, Zhu Y, Neuzil KM, Fairchok MP, Englund JA. Trivalent inactivated influenza vaccine (TIV) immunogenicity in children 6 through 23 months of age: do children of all ages respond equally? Vaccine. 2010; 28:4376–83.

15. Seidman JC, Richard SA, Viboud C, Miller MA. Quantitative review of antibody response to inactivated seasonal influenza vaccines. Influenza Other Respir Viruses. 2012; 6:52–62.

16. Langley JM, Vanderkooi OG, Garfield HA, Hebert J, Chandrasekaran V, Jain VK, et al. Immunogenicity and safety of 2 dose levels of a thimerosal-free trivalent seasonal influenza vaccine in children aged 6–35 months: a randomized, controlled trial. J Pediatric Infect Dis Soc. 2012; 1:55–63.

17. Yang P, Thompson MG, Ma C, Shi W, Wu S, Zhang D, et al. Influenza vaccine effectiveness against medically-attended influenza illness during the 2012–2013 season in Beijing, China. Vaccine. 2014; 32:5285–9.

18. Song JY, Ha SH, Kee SY, Jeong HW, Cheong HJ, Kim WJ. Debate on annual influenza vaccination in healthcare workers for the same subtype under the vaccine shortage. J Clin Virol. 2007; 38:149–52.

19. Ahout I, Ferwerda G, de Groot R. Influenza vaccination in kids, are you kidding me? J Infect. 2014; 68(Suppl 1):S100–7.

20. Heinonen S, Silvennoinen H, Lehtinen P, Vainionpaa R, Ziegler T, Heikkinen T. Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: an observational cohort study. Lancet Infect Dis. 2011; 11:23–9.

21. Blyth CC, Jacoby P, Effler PV, Kelly H, Smith DW, Robins C, et al. Effectiveness of trivalent flu vaccine in healthy young children. Pediatrics. 2014; 133:e1218–25.

22. Kee SY, Lee JS, Cheong HJ, Chun BC, Song JY, Choi WS, et al. Influenza vaccine coverage rates and perceptions on vaccination in South Korea. J Infect. 2007; 55:273–81.

23. Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demi cheli V. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2008; 2:CD004879.

24. Neuzil KM, Edwards KM. Influenza vaccines in children. Semin Pediatr Infect Dis. 2002; 13:174–81.

25. McMahon AW, Iskander J, Haber P, Chang S, Woo EJ, Braun MM, et al. Adverse events after inactivated influenza vaccination among children less than 2 years of age: analysis of reports from the vaccine adverse event reporting system, 1990–2003. Pediatrics. 2005; 115:453–60.

26. Kanra G, Marchisio P, Feiterna-Sperling C, Gaedicke G, Lazar H, Durrer P, et al. Comparison of immunogenicity and tolerability of a virosome-adjuvanted and a split influenza vaccine in children. Pediatr Infect Dis J. 2004; 23:300–6.

27. Jo YM, Ki SY, Song JY, Choi WS, Kim JY, Seo YB, et al. Immunogenicity and safety of half dose intradermal injection compared to full dose intramuscular injection of influenza vaccine in healthy adults. Infect Chemother. 2006; 38:259–65.

28. Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gitt-leson C, Bennet J, et al. Response to a monovalent 2009 in fluenza A (H1N1) vaccine. N Engl J Med. 2009; 361:2405–13.

29. al-Mazrou A, Scheifele DW, Soong T, Bjornson G. Comparison of adverse reactions to whole-virion and split-virion influenza vaccines in hospital personnel. CMAJ. 1991; 145:213–8.

30. Kim YK, Eun BW, Kim NH, Kang EK, Lee BS, Kim DH, et al. Comparison of immunogenicity and reactogenicity of split versus subunit influenza vaccine in Korean children aged 6–35 months. Scand J Infect Dis. 2013; 45:460–8.

31. Masurel N, Ophof P, de Jong P. Antibody response to immunization with influenza A/USSR/77 (H1N1) virus in young individuals primed or unprimed for A/New Jersey/76 (H1N1) virus. J Hyg (Lond). 1981; 87:201–9.

Table 1.

Demographic Characteristics

Characteristic	Total subjects (n=65)
Age
6–59 mo	31 (47.7)
5–18 yr	34 (52.3)
Mean age (yr)	5.9±4.1
Sex
Male	33 (50.8)
Female	32 (59.2)
Pre-vaccination history
Primed	57 (87.7)
Unprimed	8 (12.3)

Values are presented as number (%) or mean±standard deviation.

Table 2.

Immunogenicity of Subjects

	A/H1N1	A/H3N2	B C	CPMP standards
Seroprotection rate (%)	87.7	89.2	89.2	≥70%
Seroconversion rate (%)	44.6	73.8	63.1	≥40%
GMT ratio	4.5	8.4	10.5	>2.5-fold

Abbreviation: CPMP, committee for proprietary medicinal products; GMT, geometric mean titer.

Table 3.

Comparison of Immunogenicity of Influenza Vaccine According to Age Groups

	6–59 mo (n=31)	5–18 yr (n=34)	Total (n=65)	Pvalue
H1N1
Pre-vaccination HI Ab ≥1:40 (%)	11 (35.5)	25 (73.5)	36 (55.4)	<0.001
Post-vaccination HI Ab ≥1:40 (%)	25 (80.6)	32 (94.1)	57 (87.7)	0.021
Seroconversion (%)	16 (51.6)	13 (38.2)	29 (44.6)	0.398
Pre-vaccination GMT	20.0	72.0	38.3	0.015
Post-vaccination GMT	134.5	219.3	172.4	0.329
GMT ratio	6.7	3.0	4.5	0.026
H3N2
Pre-vaccination HI Ab ≥1:40 (%)	10 (32.3)	20 (58.8)	30 (46.1)	0.017
Post-vaccination HI Ab ≥1:40 (%)	26 (83.9)	32 (94.1)	58 (89.2)	0.042
Seroconversion (%)	25 (80.6)	23 (67.6)	48 (73.8)	0.620
Pre-vaccination GMT	16.8	36.0	27.8	0.194
Post-vaccination GMT	170.7	313.3	232.4	0.107
GMT ratio	8.5	8.7	8.4	0.284
B
Pre-vaccination HI Ab ≥1:40 (%)	5 (16.1)	18 (52.9)	23 (35.4)	<0.001
Post-vaccination HI Ab ≥1:40 (%)	26 (83.9)	32 (94.1)	58 (89.2)	0.042
Seroconversion (%)	23 (74.2)	18 (52.9)	41 (63.1)	0.152
Pre-vaccination GMT	8.8	33.1	17.2	0.004
Post-vaccination GMT	128.8	248.7	179.9	0.126
GMT ratio	6.4	7.5	10.5	0.024

Values are presented as number (%).

GMT ratio is defined as division of post-GMT by pre-GMT.

Abbreviations: HI, hemagglutinin inhibition; GMT, geometric mean titer.

Table 4.

Comparison of Immunogenicity of Influenza Vaccine between Primed and Unprimed Group

	Primed (n=57)	Unprimed (n=8)	P-value
H1N1
Pre-vaccination HI Ab ≥1:40 (%)	34 (59.6)	2 (25.0)	0.065
Post-vaccination HI Ab ≥1:40 (%)	52 (91.2)	5 (62.5)	0.021
Seroconversion (%)	24 (42.1)	5 (62.5)	0.284
Pre-vaccination GMT	43.6	15.4	0.305
Post-vaccination GMT	180.7	123.4	0.370
GMT ratio	4.1	8.0	0.405
H3N2
Pre-vaccination HI Ab ≥1:40 (%)	28(49.1)	2 (25.0)	0.200
Post-vaccination HI Ab ≥1:40 (%)	50 (87.7)	8 (100.0)	0.294
Seroconversion (%)	41 (71.9)	8 (100.0)	0.084
Pre-vaccination GMT	27.8	10.9	0.153
Post-vaccination GMT	224.9	293.4	0.588
GMT ratio	8.1	26.9	0.033
B
Pre-vaccination HI Ab ≥1:40 (%)	22 (38.6)	1 (12.5)	0.148
Post-vaccination HI Ab ≥1:40 (%)	51 (89.5)	7 (87.5)	0.866
Seroconversion (%)	34 (59.6)	7 (87.5)	0.126
Pre-vaccination GMT	19.3	7.7	0.140
Post-vaccination GMT	174.2	226.3	0.610
GMT ratio	9.0	29.4	0.059

Values are presented as number (%).

GMT ratio is defined as division of post-GMT by pre-GMT.

Abbreviations: HI, hemagglutinin inhibition; GMT, geometric mean titer.

Table 5.

Local and Systemic Adverse Events

	Total (n=65)	Age			Pre-vaccination status
	Total (n=65)	6–59 mo (n=31)	5–18 yr (n=34)	P-value	Primed (n=57)	Unprimed (n=8)	P-value
Subjects experiencing local reactions (%)	42 (64.6)	14 (45.1)	28 (82.3)	<0.001	41 (71.9)	2 (25.0)	0.008
Redness	32 (49.2)	6	17	0.268	31	1	0.026
Pain	28 (43.1)	3	13	<0.001	27	1	0.042
Swelling	27 (41.5)	2	15	0.026	27	0	0.013
Subjects experiencing systemic reactions (%)	26 (40.0)	8 (25.8)	18 (52.9)	0.007	24 (42.1)	4 (50.0)	0.679
Fever	5 (7.7)	3	2	0.573	4	1	0.593
Chill	6 (9.2)	1	5	0.114	6	0	0.343
Fatigue	15 (23.1)	3	12	0.014	13	2	0.892
Headache	7 (10.8)	0	7	0.003	7	0	0.265
Myalgia	13 (20.0)	3	10	0.026	12	1	0.809
Arthralgia	7 (10.8)	0	7	0.007	7	0	0.301
Subjects experiencing ADE (%)	48 (73.8)	17 (54.8)	31 (91.2)	<0.001	48 (84.2)	4 (50.0)	0.077

Values are presented as number (%).

Abbreviation: ADE, adverse drug event.

TOOLS

Similar articles