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Title: Characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and Mycoplasma hyopneumoniae vaccines

Author
item GALLIHER-BECKLEY, A - Kansas State University
item PAPPAN, L - Kansas State University
item MADERA, RACHEL - Kansas State University
item BURAKOVA, Y - Kansas State University
item WATERS, A - Kansas State University
item NICKLES, M - Kansas State University
item LI, X - Kansas State University
item NIETFELD, J - Kansas State University
item SCHLUP, JR - Kansas State University
item ZHONG, Q - University Of Tennessee
item McVey, David
item DRITZ, S - Kansas State University
item SHI, J - Kansas State University

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/2015
Publication Date: 6/9/2015
Citation: Galliher-Beckley, A., Pappan, L.K., Madera, R., Burakova, Y., Waters, A., Nickles, M., Li, X., Nietfeld, J., Schlup, J., Zhong, Q., Mcvey, D.S., Dritz, S.S., Shi, J. 2015. Characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and Mycoplasma hyopneumoniae vaccines. Vaccine. 33:2903-2908. doi: 10.1016/j.vaccine.2015.04.065

Interpretive Summary: Although attenuated live organisms are frequently used as vaccines to control infectious diseases, these modified live vaccines (MLV) may pose potential safety risks when administered to immune-compromised animals or the virus/bacteria is capable of reverting to a virulent form. The incorporation of an adjuvant into a vaccine can achieve qualitative and quantitative alteration of the immune protection and provide functionally appropriate types of immune responses. Adjuvants also act to reduce the antigen dose required to generate a protective response and extend the duration of effective immunity. Adjuvants can be broadly divided into two categories, the first being antigen vehicles, such as emulsions and liposomes, which act to present vaccine antigens to the immune system in a more efficient way and prolong the release of antigens to increase the specific immune responses. The second category of adjuvants are immuno-stimulants, such as Toll-like receptor (TLR) agonists, aluminum hydroxide, saponins and cytokines. One major limiting factor of adjuvants is that many of them have unaccept-able side effects and lack of biocompatibility. However, recent reports suggest that some adjuvants lack efficacy for several pathogens. Conventional oil-in-water emulsions use various chemical emulsifiers (i.e. Tween 80 and Span 80), but the safety of these chemicals when injected intramuscularly remains controversial. Herein, we use food-grade plant-derived surfactants commonly used inhuman food processing as emulsifiers to stabilize a novel oil-in-water emulsion, referred to as OW-14. OW-14 uses inexpensive, readily available materials, is stable at temperatures up to 40'C,and can be autoclaved for sterilization. Furthermore, OW-14, when mixed with whole inactivated swine influenza and mycoplasma antigens can elicit higher and prolonged antibody responses as compared to commercial vaccines for the same pathogens. Here, we provide evidence that OW-14 emulsion is a low-cost, easy-to-use alternative adjuvant for use in swine vaccines. Vaccinated pigs developed high and prolonged antibody titers to both SIV and M. hyo.

Technical Abstract: Vaccines consisting of subunit or inactivated bacteria/virus and potent adjuvants are widely used to control and prevent infectious diseases. Because inactivated and subunit antigens are often less antigenic than live microbes, a growing need exists for the development of new and improved vaccine adjuvants that can elicit rapid and long-lasting immunity. Here we describe the development and characterization of a novel oil-in-water emulsion, OW-14. OW-14 contains low-cost plant-based emulsifiers and was added to antigen at a ratio of 1:3 with simple hand mixing. OW-14 was stable for prolonged periods of time at temperatures ranging from 4 to 40'C and could be sterilized by autoclaving. Our results showed that OW-14 adjuvanted, inactivated swine influenza viruses (SIV; H3N2 and H1N1) and Mycoplasma hyopneumoniae(M. hyo) vaccines could be safely administered to piglets in two doses, three weeks apart. Injection sites were monitored and no adverse reactions were observed. Vaccinated pigs developed high and prolonged antibody titers to both SIV and M. hyo. Interestingly, antibody titers were either comparable or greater than those produced by commercially available FluSure (SIV) or RespiSure (M. hyo) vaccines. We also found that OW-14 can induce high antibody responses in pigs that were vaccinated with a decreased antigen dose. This study provides direct evidence that we have developed an easy-to-use and low-cost emulsion that can act as a powerful adjuvant in two common types of swine vaccines.