A five year randomized controlled trial to assess the efficacy and antibody responses of a commercial and autogenous vaccine for the prevention of infectious bovine keratoconjunctivitis

Authors: HILLE, MATTHEW - University Of Nebraska; SPANGLER, MATTHEW - University Of Nebraska; Clawson, Michael - Mike; HEATH, KELLY - University Of Nebraska; VU, HIEP - University Of Nebraska; ROGERS, RACHEL - University Of Nebraska; LOY, JOHN - University Of Nebraska

Submitted to: Vaccines
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2022
Publication Date: 6/9/2022
Citation: Hille, M.M., Spangler, M.L., Clawson, M.L., Heath, K.D., Vu, H.L.X., Rogers, R.E.S., Loy, J.D. 2022. A five year randomized controlled trial to assess the efficacy and antibody responses of a commercial and autogenous vaccine for the prevention of infectious bovine keratoconjunctivitis. Vaccines. 10(6). Article 916. https://doi.org/10.3390/vaccines10060916.
DOI: https://doi.org/10.3390/vaccines10060916

Interpretive Summary: Infectious bovine keratoconjunctivitis (IBK), also known as pinkeye, is the most common eye disease of cattle in the world. Signs of IBK include light sensitivity, tearing or watering of the eye, twitching of the eyelid, and swelling of the conjunctiva which is a mucous membrane that covers the white of the eyes and the inside of eyelids. In severe cases, IBK can cause sores on the eye surface, eyeball swelling and rupture, and permanent blindness. IBK is a painful disease and cattle afflicted with bad cases of it tend to eat less and have reduced weight gain. IBK costs the United States hundreds of millions of dollars each year from treatment costs and production losses. Thus, it is important to protect cattle from acquiring IBK with vaccines and other intervention methods. While multiple bacteria are associated with IBK, just one species, Moraxella bovis has been shown to cause it in experimental studies. Thus, M. bovis is a frequent target of vaccines directed at preventing IBK. To have value to the cattle industry, these vaccines need to be effective under field conditions. In this five-year study, two types of IBK vaccines were tested on beef cattle under field conditions. One vaccine contained eight inactivated strains of M. bovis. Another was an autogenous vaccine, meaning it was produced with strains of bacteria that were specifically being carried by the cattle population, which included M. bovis and two other pathogens that are associated with IBK, Moraxella bovoculi and Mycoplasma bovoculi. A group of control cattle was also included that did not receive either vaccine. Each year for five years, cattle were randomly assigned to either the vaccine or control groups, and IBK case rates were compared between them for three of the years. The other two years were so low in IBK overall, they were not included for comparisons between the groups. Additionally, an assay was developed and used to measure the serological immune response of cattle in each group to pilin, which is a known virulence factor of M. bovis involved in attachment to the eye. Of the two vaccine groups, just the autogenous one generated a significantly stronger immunological response against pilin versus the control group. Additionally, only the autogenous vaccine group trended towards less IBK cases, however, the trend was not significant versus the control group. Thus, neither vaccine group significantly outperformed the control group in reducing IBK cases, despite the stronger immune response against pilin observed in the autogenous vaccine group. These results indicate that there is a need for the development of better, more effective next generation vaccines against M. bovis to protect cattle from IBK in the field.

Technical Abstract: A randomized control trial was performed over a five year period to assess the efficacy and antibody response induced by autogenous and commercial vaccine formulations against infectious bovine keratoconjunctivitis (IBK). Calves were randomly assigned each year to one of three arms: an autogenous vaccine treatment that included Moraxella bovis (M. bovis), Moraxella bovoculi, and Mycoplasma bovoculi antigens, a commercial M. bovis vaccine treatment, or a sham vaccine treatment that consisted only of adjuvant. A total of 1,198 calves were enrolled in the study. Calves were administered the vaccines according to label directions approximately 21 days apart, just prior to turnout on summer pastures. Treatment effects were analyzed for IBK incidence, retreatment incidence, 205-day adjusted weaning weights, and antibody response to the type IV pilus protein (pili) of M. bovis as measured by a novel indirect enzyme linked immunosorbent screening assay (ELISA). Calves vaccinated with the autogenous formulation experienced a decreased cumulative incidence of IBK over the entire study compared to those vaccinated with the commercial and sham formulations (24.5% vs 30.06% vs 30.3% respectively, p=0-.25), and had less IBK cases that required retreatment compared to the commercial and sham formulations (21.4% vs 27.9% vs 34.3% respectively, p=0.15), but these differences were not significant. The autogenous formulation induced a significantly stronger antibody response than the commercial (p=0.022) and sham formulations (p=0.001), but antibody levels were not significantly correlated with IBK protection (p=0.37).