A single dose of vero cell-derived Japanese encephalitis (JE) vaccine (Ixiaro) effectively boosts immunity in travelers primed with mouse brain-derived JE vaccines

Elina O Erra, Helena Hervius Askling, Lars Rombo, Jukka Riutta, Sirkka Vene, Sutee Yoksan, Lars Lindquist, Sari H Pakkanen, Eili Huhtamo, Olli Vapalahti, Anu Kantele, Elina O Erra, Helena Hervius Askling, Lars Rombo, Jukka Riutta, Sirkka Vene, Sutee Yoksan, Lars Lindquist, Sari H Pakkanen, Eili Huhtamo, Olli Vapalahti, Anu Kantele

Abstract

Background: A significant part of the world population lives in areas with endemic Japanese encephalitis (JE). For travelers from nonendemic countries, Vero cell-derived vaccine (JE-VC; Ixiaro) has replaced traditional mouse brain-derived vaccines (JE-MB) associated with safety concerns. The 2 vaccines are derived from different viral strains: JE-VC from the SA14-14-2 strain and JE-MB from the Nakayama strain. No data exist regarding whether JE-VC can be used to boost immunity after a primary series of JE-MB; therefore, a primary series of JE-VC has been recommended to all travelers regardless of previous vaccination history.

Methods: One hundred twenty travelers were divided into 4 groups: Volunteers with no prior JE vaccination received primary immunization with (group 1) JE-MB or (group 2) JE-VC, and those primed with JE-MB received a single booster dose of (group 3) JE-MB or (group 4) JE-VC. Immune responses were tested before and 4-8 weeks after vaccination using plaque reduction neutralization test (PRNT) against both vaccine strains.

Results: In vaccine-naive travelers, the vaccination response rate for test strains Nakayama and SA14-14-2 was 100% and 87% after primary vaccination with JE-MB and 87% and 94% after JE-VC, respectively. Antibody levels depended on the target virus, with higher titers against homologous than heterologous PRNT(50) target strain (P < .001). In travelers primed with JE-MB, vaccination response rates were 91% and 91%, and 98% and 95% after a booster dose of JE-MB or JE-VC, respectively. Subgroup analysis revealed that a higher proportion of primed (98%/95%) than nonprimed (39%/42%) volunteers responded to a single dose of JE-VC (P < .001).

Conclusions: A single dose of JE-VC effectively boosted immunity in JE-MB-primed travelers. Current recommendations should be reevaluated.

Clinical trials registration: NCT01386827.

Figures

Figure 1.
Figure 1.
A, Study groups. Group MB and group VC consisted of JE vaccine–naive travelers who received a primary vaccination series of JE-MB or JE-VC, respectively. Groups MB-MB and MB-VC consisted of travelers previously primed with JE-MB who were administered a single booster dose of JE-MB or JE-VC, respectively. The numbers of subjects enrolled in each group are indicated in the figure. A total of 38 subjects were excluded before analyses due to protocol violations: 11 in group MB, 14 in VC, 6 in MB-MB, and 7 in MB-VC. B, Timing of vaccinations and serum samples. aA subgroup of group VC provided an extra serum sample 1 month after the first vaccine dose. Abbreviations: JE, Japanese encephalitis; MB, mouse brain–derived vaccine; VC, Vero cell–derived vaccine.
Figure 2.
Figure 2.
Immune response to primary vaccination with JE vaccines in adult travelers: PRNT50 titers (reciprocal of the serum dilution that reduced the virus plaque count by 50% compared with the virus-only controls) are shown before and 4–8 weeks after a vaccination series of JE-MB (group MB; n = 15) or JE-VC (group VC; n = 31). Abbreviations: JE, Japanese encephalitis; MB, mouse brain–derived vaccine; VC, Vero cell–derived vaccine.
Figure 3.
Figure 3.
Immune response to booster vaccination with JE vaccines in adult travelers previously primed with JE-MB: PRNT50 titers (reciprocal of the serum dilution that reduced the virus plaque count by 50% compared with the virus-only controls) are shown before and 4–8 weeks after a booster dose of JE-MB (group MB-MB; n = 32) or JE-VC (group MB-VC; n = 42). Abbreviations: JE, Japanese encephalitis; MB, mouse brain–derived vaccine; VC, Vero cell–derived vaccine.

References

    1. World Health Organization. Japanese encephalitis vaccines. Wkly Epidemiol Rec. 2006;81:331–40.
    1. Pan XL, Liu H, Wang HY, et al. Emergence of genotype I of Japanese encephalitis virus as the dominant genotype in Asia. J Virol. 2011;85:9847–53.
    1. Li MH, Fu SH, Chen WX, et al. Genotype V Japanese encephalitis virus is emerging. PLoS Negl Trop Dis. 2011;5:e1231.
    1. Solomon T. Control of Japanese encephalitis—within our grasp? N Engl J Med. 2006;355:869–71.
    1. Hills SL, Griggs AC, Fischer M. Japanese encephalitis in travelers from non-endemic countries, 1973–2008. Am J Trop Med Hyg. 2010;82:930–6.
    1. Buhl MR, Lindquist L. Japanese encephalitis in travelers: review of cases and seasonal risk. J Travel Med. 2009;16:217–9.
    1. Shlim DR, Solomon T. Japanese encephalitis vaccine for travelers: exploring the limits of risk. Clin Infect Dis. 2002;35:183–8.
    1. Fischer M, Lindsey N, Staples JE, Hills S Centers for Disease Control and Prevention (CDC) Japanese encephalitis vaccines: recommendations of the advisory committee on immunization practices (ACIP) MMWR Recomm Rep. 2010;59:1–27.
    1. Wilder-Smith A, Halstead SB. Japanese encephalitis: update on vaccines and vaccine recommendations. Curr Opin Infect Dis. 2010;23:426–31.
    1. Lindsey NP, Staples JE, Jones JF, et al. Adverse event reports following Japanese encephalitis vaccination in the United States, 1999–2009. Vaccine. 2010;29:58–64.
    1. Plesner AM, Arlien-Soborg P, Herning M. Neurological complications to vaccination against Japanese encephalitis. Eur J Neurol. 1998;5:479–85.
    1. Ohtaki E, Matsuishi T, Hirano Y, Maekawa K. Acute disseminated encephalomyelitis after treatment with Japanese B encephalitis vaccine (Nakayama-Yoken and Beijing strains) J Neurol Neurosurg Psychiatry. 1995;59:316–7.
    1. Andersen MM, Ronne T. Side-effects with Japanese encephalitis vaccine. Lancet. 1991;337:1044.
    1. Ruff TA, Eisen D, Fuller A, Kass R. Adverse reactions to Japanese encephalitis vaccine. Lancet. 1991;338:881–2.
    1. Sakaguchi M, Miyazawa H, Inouye S. Specific IgE and IgG to gelatin in children with systemic cutaneous reactions to Japanese encephalitis vaccines. Allergy. 2001;56:536–9.
    1. Tauber E, Kollaritsch H, Korinek M, et al. Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial. Lancet. 2007;370:1847–53.
    1. Tauber E, Kollaritsch H, von Sonnenburg F, et al. Randomized, double-blind, placebo-controlled phase 3 trial of the safety and tolerability of IC51, an inactivated Japanese encephalitis vaccine. J Infect Dis. 2008;198:493–9.
    1. Schuller E, Jilma B, Voicu V, et al. Long-term immunogenicity of the new Vero cell-derived, inactivated Japanese encephalitis virus vaccine IC51 six and 12 month results of a multicenter follow-up phase 3 study. Vaccine. 2008;26:4382–6.
    1. Dubischar-Kastner K, Eder S, Buerger V, et al. Long-term immunity and immune response to a booster dose following vaccination with the inactivated Japanese encephalitis vaccine IXIARO, IC51. Vaccine. 2010;28:5197–202.
    1. Eder S, Dubischar-Kastner K, Firbas C, et al. Long term immunity following a booster dose of the inactivated Japanese encephalitis vaccine IXIARO, IC51. Vaccine. 2011;29:2607–12.
    1. Dubischar-Kastner K, Kaltenboeck A, Klingler A, Jilma B, Schuller E. Safety analysis of a Vero-cell culture derived Japanese encephalitis vaccine, IXIARO (IC51), in 6 months of follow-up. Vaccine. 2010;28:6463–9.
    1. Schuller E, Klingler A, Dubischar-Kastner K, Dewasthaly S, Muller Z. Safety profile of the Vero cell-derived Japanese encephalitis virus (JEV) vaccine IXIARO. Vaccine. 2011;29:8669–76.
    1. Centers for Disease Control and Prevention (CDC) Recommendations for use of a booster dose of inactivated Vero cell culture-derived Japanese encephalitis vaccine: advisory committee on immunization practices, 2011. MMWR Morb Mortal Wkly Rep. 2011;60:661–3.
    1. Russell PK, Nisalak A, Sukhavachana P, Vivona S. A plaque reduction test for dengue virus neutralizing antibodies. J Immunol. 1967;99:285–90.
    1. Hombach J, Solomon T, Kurane I, Jacobson J, Wood D. Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2–3 September, 2004. Vaccine. 2005;23:5205–11.
    1. Hoke CH, Nisalak A, Sangawhipa N, et al. Protection against Japanese encephalitis by inactivated vaccines. N Engl J Med. 1988;319:608–14.
    1. Henderson A. Immunisation against Japanese encephalitis in Nepal: experience of 1152 subjects. J R Army Med Corps. 1984;130:s188–91.
    1. Poland JD, Cropp CB, Craven RB, Monath TP. Evaluation of the potency and safety of inactivated Japanese encephalitis vaccine in US inhabitants. J Infect Dis. 1990;161:878–82.
    1. Sanchez JL, Hoke CH, McCown J, et al. Further experience with Japanese encephalitis vaccine. Lancet. 1990;335:972–3.
    1. Gambel JM, DeFraites R, Hoke C, Jr, et al. Japanese encephalitis vaccine: persistence of antibody up to 3 years after a three-dose primary series. J Infect Dis. 1995;171:1074.
    1. Defraites RF, Gambel JM, Hoke CH, Jr, et al. Japanese encephalitis vaccine (inactivated, BIKEN) in U.S. soldiers: immunogenicity and safety of vaccine administered in two dosing regimens. Am J Trop Med Hyg. 1999;61:288–93.
    1. Hanna JN, Smith GA, McCulloch BG, Taylor CT, Pyke AT, Brookes DL. An assessment of the interval between booster doses of Japanese encephalitis vaccine in the Torres Strait. Aust N Z J Public Health. 2005;29:44–7.
    1. Kurane I, Takasaki T. Immunogenicity and protective efficacy of the current inactivated Japanese encephalitis vaccine against different Japanese encephalitis virus strains. Vaccine. 2000;18(suppl 2):33–5.
    1. Ferguson M, Johnes S, Li L, Heath A, Barrett A. Effect of genomic variation in the challenge virus on the neutralization titres of recipients of inactivated JE vaccines—report of a collaborative study on PRNT50 assays for Japanese encephalitis virus (JE) antibodies. Biologicals. 2008;36:111–6.
    1. Schuller E, Klade CS, Heinz FX, et al. Effect of pre-existing anti-tick-borne encephalitis virus immunity on neutralising antibody response to the Vero cell-derived, inactivated Japanese encephalitis virus vaccine candidate IC51. Vaccine. 2008;26:6151–6.
    1. Kaltenbock A, Dubischar-Kastner K, Eder G, et al. Safety and immunogenicity of concomitant vaccination with the cell-culture based Japanese encephalitis vaccine IC51 and the hepatitis A vaccine HAVRIX1440 in healthy subjects: a single-blind, randomized, controlled phase 3 study. Vaccine. 2009;27:4483–9.

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