Suppository-Mediated DNA Immunization Induces Mucosal Immunity against Bovine Herpesvirus-1 in Cattle

Abstract

Mucosal surfaces are the primary sites for the transmission of infectious agents including viruses, so effective vaccines generally should induce mucosal immunity. Furthermore, noninvasive delivery is desirable because of the ease of application, the high degree of patient compliance, and the improved safety for patients and clinicians due to the elimination of needles. Unfortunately, most of the conventional vaccines are parenterally administered and result in systemic rather than mucosal immunity. Here we present the first report of mucosal immunity by noninvasive DNA immunization in a target species. As an approach to induce mucosal immunity against bovine herpesvirus-1, cows were immunized intravaginally with suppositories containing plasmid coding for glycoprotein D. Serum IgG, as well as IgA both in the serum and in the nasal fluids, were detected, which supports the contention of a common mucosal immune system. This level of immunity was of sufficient magnitude to minimize weight loss and significantly reduce the duration of virus shedding after intranasal viral challenge, which demonstrates the efficacy of suppository-based administration of DNA vaccines to target species. As this is a very practical method of delivery, it has great potential to be applied as vaccine or therapy in a variety of species.

Genetic immunisation of cattle against Bovine herpesvirus 1: glycoprotein gD confers higher protection than glycoprotein gC or tegument protein VP8

“…Different routes of DNA administration to cattle have been tested such as intradermic or intramuscular injection [10,17,54] and biolistic delivery (gene-gun) of gold particles coated with DNA vaccines [6,33,34]. Mucosal administration of plasmid DNA via a gene-gun [34] or into suppositories [35] has also been shown to induce systemic as well as mucosal immunity.…”

Modulation of immune responses to bovine herpesvirus‐1 in cattle by immunization with a DNA vaccine encoding glycoprotein D as a fusion protein with bovine CD154

“…In comparison to other BHV‐1 glycoproteins, gD is most effective at providing protection against BHV‐1 infection 11 . Advances in plasmid design and optimization of immunization parameters have resulted in the induction of strong gD‐specific cellular immune responses by gD‐expressing plasmids in cattle 12–15 . However, significant improvements in the kinetics and magnitude of the antibody responses have yet to be accomplished.…”

Challenges in mucosal vaccination of cattle

“…Similar mechanisms for antigen acquisition exist at other mucosal sites, including in tonsilar crypts and in BALT where both M cells and epithelial DCs have been identified (Gebert and Pabst, 1999;Stanley et al, 2001), and presumably also at genital sites (Hodgins et al, 2005). Experimentally, calves have been immunized by the vulvovaginal and rectal routes (Loehr et al, 2000(Loehr et al, , 2001, but most mucosal vaccines deliver antigens by oral administration, which targets intestinal induction, or intranasally which targets pharyngeal and, depending on particle size, deeper respiratory tissues.…”