Evaluation of protective and immune responses following vaccination with recombinant MIP and CPAF from Chlamydia abortus as novel vaccines for enzootic abortion of ewes

Authors: O'NEILL, LAURENM - University College Dublin; KEANE, ORLA - Teagasc (AGRICULTURE AND FOOD DEVELOPMENT AUTHORITY); ROSS, PADRAIG - Department Of Agriculture, Food, And The Marine; Nally, Jarlath; SESHU, JANAKARIM - University Of Texas At San Antonio; MARKEY, BRYAN - University College Dublin

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/1/2019
Publication Date: 8/8/2019
Citation: O'Neill, L., Keane, O.M., Ross, P.J., Nally, J.E., Seshu, J., Markey, B.K. 2019. Evaluation of protective and immune responses following vaccination with recombinant MIP and CPAF from Chlamydia abortus as novel vaccines for enzootic abortion of ewes. Vaccine. 37(36):5428-5438. https://doi.org/10.1016/j.vaccine.2019.06.088.
DOI: https://doi.org/10.1016/j.vaccine.2019.06.088

Interpretive Summary: Enzootic abortion of ewes (EAE) is caused by the bacterial pathogen Chlamydia abortus. EAE is one of the most prevalent causes of infectious ovine abortion worldwide. Currently recommended control efforts in the face of abortion outbreaks are based on the prophylactic use of long-acting tetracycline antibiotics and the use either of a live attenuated vaccine or a killed vaccine to limit the spread of the infection from animal to animal. However, studies have found instances outbreaks of abortions occurring in vaccinated flocks that could be traced back to the vaccine strain administered. Therefore, it is clear that there is a great need for safer vaccines to control this common and important disease. Our previous work identified proteins of C. abortus that interact directly with the host during infection. In this work, we assessed the ability of two of these proteins, named MIP and CPAF, to act as a vaccine in the prevention of EAE. When used in combination, these two proteins had a 50% vaccine efficacy rate. Results demonstrate the potential of subunit recombinant proteins as vaccines for EAE prevention.

Technical Abstract: MIP and CPAF from Chlamydia have been shown to be effective in inducing immune responses important in clearing chlamydial infections. This study evaluates the protection conferred by MIP and CPAF as novel vaccines in pregnant C. abortus challenged ewes. Fifty C. abortus sero-negative sheep were randomly allocated into 5 groups of 10 according to the treatment they were to receive (1) 100 mu g of MBP-MIP (2) 100 mu g CPAF (3) 50 mu g MBP-MIP and 50 mu g CPAF (4) Tris-buffer (negative control) (5) Enzovax (positive control). Booster inoculations were administered 3 weeks after primary inoculations. Blood samples were taken pre-vaccination and weekly for 5 weeks. Five months after vaccination the ewes were mated. Pregnant ewes were then challenged on day 90 of gestation. Blood samples taken at four time-points post challenge were analysed for IFN' levels, TNFa and IL-10 expression and anti-chlamydial antibody levels. Vaginal swabs, placental and foetal tissue and bacterial shedding were analysed using qPCR to quantify levels of C. abortus. Enzovax was 100% effective with no abortions occurring. The MIP/CPAF combined vaccine offered the greatest protection of the novel vaccines with 67% of ewes giving birth to one or more live lambs equating to a 50% vaccine efficacy rate. MIP and CPAF administered singly did not confer protection. Enzovax and MIP/CPAF vaccinated ewes had longer gestations and lambs with higher birth weights than negative control ewes. Aborting ewes shed higher numbers of C. abortus than ewes that had live lambs, all vaccinated ewes demonstrated lower levels of bacterial shedding than negative control ewes with Enzovax ewes shedding significantly fewer bacteria. Ewes that went on to abort had significantly higher levels of IFN' and IL-10 at 43 day 35 post challenge and significantly higher levels of anti-chlamydial antibodies at 24 h post lambing compared to ewes that had live lambs.