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Chimpanzees as an animal model for human norovirus infection and vaccine development.

ABSTRACT: Noroviruses are global agents of acute gastroenteritis, but the development of control strategies has been hampered by the absence of a robust animal model. Studies in chimpanzees have played a key role in the characterization of several fastidious hepatitis viruses, and we investigated the feasibility of such studies for the noroviruses. Seronegative chimpanzees inoculated i.v. with the human norovirus strain Norwalk virus (NV) did not show clinical signs of gastroenteritis, but the onset and duration of virus shedding in stool and serum antibody responses were similar to that observed in humans. NV RNA was detected in intestinal and liver biopsies concurrent with the detection of viral shedding in stool, and NV antigen expression was observed in cells of the small intestinal lamina propria. Two infected chimpanzees rechallenged 4, 10, or 24 mo later with NV were resistant to reinfection, and the presence of NV-specific serum antibodies correlated with protection. We evaluated the immunogenicity and efficacy of virus-like particles (VLPs) derived from NV (genogroup I, GI) and MD145 (genogroup II, GII) noroviruses as vaccines. Chimpanzees vaccinated intramuscularly with GI VLPs were protected from NV infection when challenged 2 and 18 mo after vaccination, whereas chimpanzees that received GII VLPs vaccine or a placebo were not. This study establishes the chimpanzee as a viable animal model for the study of norovirus replication and immunity, and shows that NV VLP vaccines could induce protective homologous immunity even after extended periods of time.

SUBMITTER: Bok K

PROVIDER: S-EPMC3017165 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Chimpanzees as an animal model for human norovirus infection and vaccine development.

Bok Karin K Parra Gabriel I GI Mitra Tanaji T Abente Eugenio E Shaver Charlene K CK Boon Denali D Engle Ronald R Yu Claro C Kapikian Albert Z AZ Sosnovtsev Stanislav V SV Purcell Robert H RH Green Kim Y KY

Proceedings of the National Academy of Sciences of the United States of America 20101220 1

Noroviruses are global agents of acute gastroenteritis, but the development of control strategies has been hampered by the absence of a robust animal model. Studies in chimpanzees have played a key role in the characterization of several fastidious hepatitis viruses, and we investigated the feasibility of such studies for the noroviruses. Seronegative chimpanzees inoculated i.v. with the human norovirus strain Norwalk virus (NV) did not show clinical signs of gastroenteritis, but the onset and d ...[more]

PMID: 21173246

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Project description:Soon after its identification, norovirus (NoV) has been indicated as one of the most common causes of outbreaks of acute gastroenteritis (AGE) and sporadic acute diarrhea episodes in subjects of any age. In 2016 the World Health Organization stated that the development of a NoV vaccine should be considered an absolute priority. Unfortunately, the development of an effective NoV vaccine has proven extremely difficult, and only in recent years, some preparations have been tested in humans in advanced clinical trials. In this paper, reasons that justify efforts to develop a NoV vaccine, difficulties encountered during NoV vaccine development, and NoV vaccine candidates will be discussed. In recent years, identification of some NoV antigens that alone or in combination with other viral antigens can induce a potentially protective immune response has led to the development of a large series of preparations that seem capable of coping with the problems related to NoV infection. Epidemiological and immunological studies have shown that multivalent vaccines, including both GI and GII NoV, are the only solution to induce sufficiently broad protection. However, even if the road to formulation of an effective and safe NoV vaccine seems to be definitively traced, many problems still need to be solved before the total burden of NoV infections can be adequately controlled. Whether currently available vaccines are able to protect against all the heterologous NoV strains and the variants of the most common serotypes that frequently emerge and cause outbreaks must be defined. Moreover, as performed clinical trials have mainly enrolled adults, it is mandatory to know whether vaccines are effective in all age groups, including younger children. Finally, we must know the immune response of immunocompromised patients and the duration of protection induced by NoV vaccines. Only when all these problems have been solved will it be possible to establish an effective immunization schedule against NoV infection and calculate whether systematic vaccination can be cost effective.

Dataset Information

Chimpanzees as an animal model for human norovirus infection and vaccine development.

Publications

Chimpanzees as an animal model for human norovirus infection and vaccine development.

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