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Journal of Virology, October 2000, p. 8966-8971, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Nasal Immunization of Mice with Virus-Like Particles Protects Offspring against Rotavirus Diarrhea

Alix Coste,1,2 Jean-Claude Sirard,1 Kari Johansen,3 Jean Cohen,4 and Jean-Pierre Kraehenbuhl1,*

Swiss Institute for Experimental Cancer Research and the Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland1; Laboratoire de Microbiologie INRA, 63122 St. Genes-Champanelle,2 and Laboratoire de Virologie et d'Immunologie Moléculaire INRA, C.R.J. Domaine de Vilvert, 78350 Jouy-en-Josas,4 France; and Department of Virology, Smyttskyddsinstitutet, Karolinska Institute, 105 21 Stockholm, Sweden3

Received 6 April 2000/Accepted 13 July 2000

Rotavirus is the major cause of diarrhea among young infants in both humans and animals. Immune protection of newborns by vaccination is difficult to achieve since there is not enough time to mount an immune response before exposure to the virus. We have designed a vaccination strategy mediating transfer of neutralizing antibodies from the mother to the offspring during pregnancy and/or lactation. Adult female mice were nasally immunized with virus-like particles (VLPs) made of viral proteins VP2 and 6 (VLP2/6) or VP 2, 6, and 7 (VLP2/6/7) derived from the RF rotavirus strain in the presence or absence of cholera toxin. Both vaccines elicited serum and milk antibodies against the respective VPs. Four days after parturition, suckling pups were challenged orally with RF rotavirus. Pups from mothers immunized with VLP2/6/7 but not VLP2/6 were protected against rotavirus diarrhea, indicating that VP7 plays a key role in protection. Protection was mediated by milk rather than serum antibodies, and mucosal adjuvants were not required. In conclusion, VLPs containing VP7 administered nasally to mothers represent a promising vaccine candidate for the protection of suckling newborns against rotavirus-induced diarrhea, even in the absence of a mucosal adjuvant.


* Corresponding author. Mailing address: ISREC, CH-1066 Epalinges, Switzerland. Phone: (41 21) 692 58 56. Fax: (41 21) 652 69 33. E-mail: Jean-Pierre.Kraehenbuhl{at}isrec.unil.ch.


Journal of Virology, October 2000, p. 8966-8971, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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