Chimeric Plant Virus Particles Administered Nasally or Orally Induce Systemic and Mucosal Immune Responses in Mice

Abstract

The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone or in the presence of ISCOM matrix, primed CPMV-specific T cells and generated high titers of CPMV-and FnBP-specific immunoglobulin G (IgG) in sera. Furthermore, CPMV-and FnBP-specific IgA and IgG could also be detected in the bronchial, intestinal, and vaginal lavage fluids, highlighting the ability of CVPs to generate antibody at distant mucosal sites. IgG2a and IgG2b were the dominant IgG subclasses in sera to both CPMV and FnBP, demonstrating a bias in the response toward the T helper 1 type. The sera completely inhibited the binding of human fibronectin to the S. aureus FnBP. Oral immunization of the CVPs also generated CPMV-and FnBP-specific serum IgG; however, these titers were significantly lower and more variable than those generated by the intranasal route, and FnBP-specific intestinal IgA was undetectable. Neither the ISCOM matrix nor cholera toxin enhanced these responses. These studies demonstrate for the first time that recombinant plant viruses have potential as mucosal vaccines without the requirement for adjuvant and that the nasal route is most effective for the delivery of these nonreplicating particles.

Antigen Delivery Systems III: Use of Recombinant Plant Viruses

“…Oral immunization was considerably less effective, with only serum antibody being stimulated in a minority of mice. Similar results were obtained when mice were immunized nasally or orally with a CPMV chimera expressing a 30-amino acid sequence from the S. aureus FnBP (Brennan et al, 1999d). Detailed characterization of the immune responses in mice immunized nasally with CPMV chimeras expressing epitopes from CPV provided further support to the idea that it will be possible to stimulate mucosal immunity by this route (Nicholas et al, 2002).…”

A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose

“…We achieved this result by intranasally delivering empty virus-like particles (VLPs), which act to modulate the lung microenvironment, and harness and focus immune responses. Recent exploration in the utilization of nanoparticles [12][13][14], virus-like particles [15][16][17][18][19][20][21], and viruses which have no mammalian cell tropism, has shown that these platforms are naturally immunostimulatory, and likely utilize evolutionarily conserved cell surface receptors, thereby safely engaging immune signaling pathways without replicating [22][23][24][25][26]. Furthermore, many of these strategies are currently on the market or undergoing clinical trials, and have already had broad global impact in safely preventing disease [21,[27][28][29].…”

Viral vectors for production of recombinant proteins in plants

“…The capability of CVPs in inducing an antibody response specifically to the displayed epitope upon intranasal, intraperitoneal or oral administration, have been extensively demonstrated in different animal models (Table 1). Other data show CVPs ability to elicit a strong specific neutralizing immune response in the absence of adjuvants (Yusibov et al, 1997; Brennan et al, 1999; Marusic et al, 2001). Oral delivery of spinach leaves infected with CVPs elicited a strong antibody response to the displayed rabies virus peptide in mice and human volunteers (Yusibov et al, 2002), indicating a potential use of this system as a supplementary oral booster for rabies vaccinations.…”