Intervirology 2002;45:328–333
(DOI:10.1159/000067925)

Review of an Inactivated Vaccine against Hantaviruses

Cho H.-W.a · Howard C.R.b · Lee H.-W.c
aDepartment of Virology, National Institute of Health, Seoul, Korea; bDepartment of Pathology and Infectious Disease, Royal Veterinary College, London, UK; cWHO Collaborating Center for Virus Reference and Research (Hantaviruses), Asan Institute for Life Science, Seoul, Korea
email Corresponding Author


 goto top of outline Key Words

  • Haemorrhagic fever with renal syndrome
  • Hantavirus
  • Neutralizing antibody

 goto top of outline Abstract

Objective: Hantaviruses cause haemorrhagic fever with renal syndrome and result in severe morbidity and mortality in humans. Safe and effective vaccines are needed to reduce the incidence of human illness. In this study, the immune response to an inactivated hantavirus vaccine was measured in 64 human volunteers for Hantavax® and 10 human volunteers for a Hantaan-Puumala virus combination vaccine at high risk of infection by virtue of their residence and occupation. Methods: A serum sample was obtained from each volunteer before the initial vaccination (day 0), 30 days after each inoculation and 1 year after the initial dose. All sera were kept at –20° until tested. IgG-specific antibody titres were tested by ELISA and immunofluorescence assay (IFA). Neutralizing antibody titres were determined by a plaque reduction neutralizing test. Results: Thirty days after vaccination, 79 and 62% of the subjects had developed a significant hantavirus antibody titre as measured by IFA and ELISA, respectively. Seroconversion rates increased to 97% 1 month after the booster dose. Neutralizing antibody titres paralleled this trend, with 13% of vaccine recipients producing neutralizing antibody 1 month after the first dose and 75% of vaccine recipients responding 1 month after boosting. Antibody titres had declined by 1 year, however, with only 37 and 43% of sera found to be positive by IFA and ELISA, respectively. Re-vaccination at this time produced a vigorous anamnestic response, with 94 and 100% of vaccine recipients yielding positive antibody titres. Only 50% of the sampled population, however, produced neutralizing antibodies following the booster dose 1 year later. Conclusions: The vaccine was well tolerated and there were no apparent differences in the responses in human subjects. However, further improvement of this vaccine is necessary in order to induce a longer-lasting humoral immune response.

Copyright © 2003 S. Karger AG, Basel


 goto top of outline References
  1. Elliott LH, Ksiazek TG, Rollin PE, Spiropoulou CF, Morzunov S, Monroe M, Goldsmith CS, Humphrey CD, Zaki SR, Krebs JW, et al: Isolation of the causative agent of hantavirus pulmonary syndrome. Am J Trop Med Hyg 1994;51:102–108.
  2. Lee HW, An CN: Development of vaccine against haemorrhagic fever with renal syndrome. J Korean Soc Virol 1988;18:143–148.
  3. Lee HW, Chu YK, Cui YS, Woo YD, An CN, Kim H, Chang YS: Immune reaction of the vaccinated hamster with combination Hantaan-puumala vaccine. J Korean Soc Virol 1997;27:39–47.
  4. French GR, Foulke RS, Brand OA, Eddy GA, Lee HW, Lee PW: Korean hemorrhagic fever: Propagation of the etiologic agent in a cell line of human origin. Science 1981;211:1046–1048.
  5. Oya A: Japanese encephalitis vaccine; the vaccination. Int Med Found Jpn 1976:69–72.
  6. Schmaljohn CS, Arikawa J, Dalrymple JM: Expression of the envelope glycoprotein of Hantaan virus with vaccina and baculo virus recombinant; in Kolakofsky D, Mahy BWJ (eds): Genetics and Pathogenicity of Negative Strand Viruses. Amsterdam, Elsevier, 1989, pp 58–66.
  7. Cho HW, Howard CR: Antibody responses in humans to an inactivated hantavirus vaccine (Hantavax®). Vaccine 1999;17:2569–2575.
  8. Lee HW, van der Groen G: Hemorrhagic fever with renal syndrome. Prog Med Virol 1989;36:62–102.
  9. Nakamura J: Studies on purified Japanese encephalitis vaccine. NIBS Bull Biol Res 1969;8:78–99.
  10. Yamanishi K, Tanishita O, Tamura M, Asada H, Kondo K, Takagi M, Yoshida I, Konobe T, Fukai K: Development of inactivated vaccine against virus causing haemorrhagic fever with renal syndrome. Vaccine 1988;6:278–282.
  11. Lee HW, Chu YK, Woo YD, An CN, Kim H, Tkachenko E, Gligic A: Vaccine against haemorrhagic fever with renal syndrome; in Saluzzo JF, Dodet B (eds): Factors in the Emergence and Control of Rodent-Borne Diseases. Paris, Elsevier, 1999, pp 267–272.

 goto top of outline Author Contacts

Hae-Wol Cho
Department of Virology, National Institute of Health
5 Nokbun Dong, Unpyung Gu
KR-Seoul (Korea)
Tel. +82 2 380 1490, Fax +82 2 382 6542, E-Mail haewolcho@yahoo.com


 goto top of outline Article Information

Number of Figures : 2, Number of Tables : 4, Number of References : 11


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)
Founded 1973 by J.L. Melnick; continued by F. Rapp (1986–1990); M.J. Buchmeier and C.R. Howard (1991–1993)

Vol. 45, No. 4-6, Year 2002 (Cover Date: July-December 2002 (Released January 2003))

Journal Editor: Rüdiger W. Braun, Stuttgart
ISSN: 0300–5526 (print), 1423–0100 (Online)

For additional information: http://www.karger.com/journals/int


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.