Home : Research : Licensable Technology : Use of an Avirulent Mutant as a Live Vaccine Vector

The respiratory tract is a target of several microorganisms that are considered potential biological terrorism threats. Historically, vaccination strategies have focused on the development of strong serum antibody titers as an indicator of efficacy. Unfortunately, serum antibody titers do not always correlate with protection. However, protective immunicity generated in response to infection is generally more effective and longer lasting than that generated in response to parenteral immunization. Thus, the concept of using live vaccines that generate immunity in a manner that is similar to infection, but that do not cause clinical disease is gaining popularity.

The subject invention is a genetically defined mutant strain of B. bronchiseptica, which is noncytotoxic in vitro and has been shown to be avirulent in vivo in mice, even in animals that are highly susceptible to Bordetellosis. It efficiently infects at low doses and is able to colonize the lower respiratory tract and nasal cavity as efficiently as its wild type parental strain. Intranasal vaccination with low doses of the strain protects mice from a subsequent challenge with wild type bacteria. Additionally, a low dose inoculation induces an immune response, as measured by antibody titers, that is indistinguishable from that induced by wild type B. bronchiseptica. Lastly, this immune response, when transferred to a naïve animal via the transfer of immune serum, is as equally protective as that generated in response to wild type bacteria.

Collectively, these results suggest that the strain is a safe and efficacious vaccine candidate that may also be used as a potential vaccine vector for the delivery of heterologous antigens. Since B. bronchiseptica strains are widely used commercially as live vaccines, there has been an extensive testing of the safety of this approach. However, current vaccines have undescribed, or undisclosed, mutations that appear to negatively affect their immunogenicity (i.e. the possibility of reversion to a more virulent form), an area in which our candidate strain has a substantial advantage.

Matthew D. Smith, Sr. Technology Licensing Officer

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