Recombinant Norwalk virus-like particles as an oral vaccine
Viruses that infect cells in the gastrointestinal tract are well suited for examining the immune response to oral delivery of antigen and for exploring the advantages and pitfalls of oral vaccines. Norwalk virus (NV) (family Caliciviridae, genus Calicivirus) causes acute gastroenteritis in all age groups. The NV capsid is composed of 180 copies of a single 58 000 molecular weight protein which spontaneously forms virus-like particles (VLPs) that can be purified in extremely high yields (22mg per 300 ml culture) when produced using the baculovirus expression system. We are testing the potential of these recombinant NV (rNV) particles for use as an oral vaccine by administering them to mice and volunteers. Mice were orally inoculated four times with rNV particles in concentrations ranging from 5 to 500 μg in the absence of adjuvant or from 5 to 200 μg with 10 μg of cholera toxin. Serum IgG and fecal IgA immune responses were monitored. rNV particles were found to be immunogenic when orally given to mice with or without adjuvant. These particles also were safe and immunogenic when orally given to volunteers. These studies show that rNV particles are an excellent model to test the oral delivery of mucosal immunogens in general, and that rNV particles are ideal candidates for vaccine development in particular.
KeywordsCholera Toxin Oral Delivery Oral Vaccine Baculovirus Expression System Oral Immunization
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- 4.Green KY, Lew JF, Jiang X, Kapikian AZ, Estes MK (1993) Comparison of the reactivities of baculovirus-expressed recombinant Norwalk virus capsid antigen with those of the native Norwalk virus antigen in serologic assays and some epidemiologic observations. J Clin Micro 31: 2185–2191Google Scholar
- 9.Kapikian AZ, Estes MK, Chanock RM (1996) Norwalk group of viruses. In: Fields BN, Knipe DM, Howley PM, Chanock RM, Melnick JL, Monath TP, Roizman B, Straus SE (eds) Virology. Raven Press, New York, pp 671–693Google Scholar