Transgenic Plant-Derived CMV Glycoprotein B Vaccine

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DESCRIPTION (provided by applicant): An innovative vaccine strategy that has been promoted in recent years is the concept of oral immunization, using transgenic plants as vaccines. The rationale for transgenic plant vaccines is based on the potential for mass productive of such vaccines; lower expense; improved mucosal immune responses; and ease of administration. Although such vaccines have been shown in animal models and in human trials to be immunogenic, there is very little data about the protective efficacy of this immunization strategy. There is similarly little information about the relative immunogenicity and efficacy of following oral administration of transgenic plant material compared with oral administration of recombinant proteins generated by more traditional expression systems. Because of perceived differences in antigen stability (conferred by the presence of a plant cell well) and immunologic processing in the gut, plant vaccines are hypothesized to be superior for oral administration. This study proposes to test this hypothesis in an animal system in which the protective immunogen is well defined. The system to be studied is the guinea pig cytomegalovirus (GPCMV) model, and the protein is the glycoprotein B (gB) protein. The rationale for choosing this protein is that this protein is clearly effective in vaccine-mediated protection against CMV disease, thus providing a valuable opportunity for testing "proof of concept" of oral vaccination. In this model, we have shown that humoral responses generated against the gB protein, when expressed as an adjuvanted subunit vaccine in baculovirus, are critical in protection of the maternal-placental-fetal unit. Furthermore, since CMV infections are typically acquired at mucosal surfaces, evaluation of recombinant gB vaccine administered at an oral vaccine, at a mucosal site, warrants investigation. Using Agrobacteria tumefaciens-mediated recombination in transgenic plant expression systems, we have engineered an Arabidopsis plant transgenic for GPCMV gB, which will be utilized to immunize guinea pigs, orally, with adjuvant (cholera toxin B), followed by GPCMV challenge during pregnancy. Oral vaccination will also be conducted with baculovirus-purified gB. We will test the hypothesis that plant-derived vaccine is more immunogenic and protective than baculovirus-derived protein when administered by an oral route. The immunogenicity and protective efficacy against congenital infection and disease of this vaccine will be evaluated. These studies will advance the field of HCMV vaccines, an important public health priority. Moreover, these studies will provide data regarding the potential efficacy of oral transgenic plant vaccination, a concept which has been subjected to relatively few efficacy analyses. Based on the rationale that gB is a key immunogen in the CMV model in guinea pigs, there is a compelling rationale to evaluate this protein as an oral plant-based vaccine, compared to oral immunization with proteins purified by other approaches. These studies will advance the fields of plant and CMV vaccines.