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Journal of Virology, July 2002, p. 6669-6677, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6669-6677.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cross-Protection against Challenge with Puumala Virus after Immunization with Nucleocapsid Proteins from Different Hantaviruses

Cristina de Carvalho Nicacio,1* Marcelo Gonzalez Della Valle,2 Paula Padula,2 Ewa Björling,1,3 Alexander Plyusnin,4,5 and Åke Lundkvist1,4

Microbiology and Tumorbiology Center, Karolinska Institutet, 171 77 Stockholm,1 Swedish Institute for Infectious Disease Control, 171 82 Solna,4 The South Hospital, Research Center, Karolinska Institutet, 118 83 Stockholm, Sweden,3 Servicio de Biología Molecular, Departamento de Virología, Instituto Nacional de Enfermedades Infecciosas, Administracion Nacional de Laboratorios e Institutos de Salud "Dr Carlos G. Malbrán," Buenos Aires, Argentina;,2 Haartman Institute, Department of Virology, University of Helsinki, Helsinki, Finland5

Received 13 November 2001/ Accepted 26 March 2002

Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. To investigate the ability of recombinant N (rN) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected. In the group immunized with DOBV rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in the group immunized with ANDV rN, which is more closely related to PUUV rN than DOBV rN. Humoral and cellular immune responses after rN immunization were also investigated. The highest cross-reactive humoral responses against PUUV antigen were detected in sera from ANDV rN-immunized animals, followed by those from TOPV rN-immunized animals, and only very low antibody cross-reactivity was observed in sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from animals immunized with all heterologous rNs were as efficiently recalled in vitro by PUUV rN as were T lymphocytes from animals immunized with homologous protein. In summary, this study has shown that hantavirus N can elicit cross-protective immune responses against PUUV, and the results suggest a more important role for the cellular arm of the immune response than for the humoral arm in cross-protection elicited by rN.

* Corresponding author. Mailing address: Microbiology and Tumorbiology Center, Box 280, Karolinska Institutet, 171 77 Stockholm, Sweden. Phone: 46 8 728 63 20. Fax: 46 8 33 07 44. E-mail: cristina.de.carvalho{at}mtc.ki.se.

Journal of Virology, July 2002, p. 6669-6677, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6669-6677.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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