Recombinant protein subunit vaccine reduces puerperal metritis incidence and modulates the genital tract microbiome

Abstract

The objective of this study was to evaluate the efficacy of 3 vaccine formulations containing proteins (FimH, leukotoxin, and pyolysin), inactivated whole cells (Escherichia coli, Fusobacterium necrophorum, and Trueperella pyogenes), or both, in the prevention of postpartum uterine diseases. A randomized clinical trial was conducted at a commercial dairy farm; 800 heifers were assigned into 1 of 4 different treatment groups: control, vaccine 1 (bacterin and subunit proteins), vaccine 2 (bacterin), and vaccine 3 (recombinant subunit proteins), and each heifer received a subcutaneous injection of its respective treatment at 240 ± 3 and 270 ± 3 d of gestation. Vaccination significantly reduced the incidence of puerperal metritis when compared with control (9.1% vs. 14.9%, respectively; odds ratio 0.51). Additionally, vaccine 3 was found to reduce the incidence of puerperal metritis when compared with the control (8.0% vs. 14.9%, respectively; odds ratio 0.46). Reproduction was improved for metritic cows that were vaccinated, and the effect was stronger for cows that were treated with vaccine 3. In general, vaccination decreased the total vaginal bacterial load and decreased the vaginal load of F. necrophorum by 9 d in milk. Vaccination reduced the prevalence of puerperal metritis in the first lactation of dairy cows, leading to less metritic disease and improved reproduction.

Recent advances and future directions for uterine diseases diagnosis, pathogenesis, and management in dairy cows

“…In recent years, three peer-reviewed studies investigated immunizations against metritis pathogens ( Freick et al., 2017 ; Machado et al., 2014 ; Meira Jr. et al., 2020 ). The first vaccine containing different combinations of proteins representing major virulence factors ( fimH ; lktA ; and pyolysin, Plo ) for uterine pathogens and/or inactivated whole cells ( Escherichia coli, Fusobacterium necrophorum, and Trueperella pyogenes ) administered either intravaginally or subcutaneously.…”

“…The third study with vaccines for metritis was a follow-up to the study 1, listed above ( Meira Jr. et al., 2020 ). It was a clinical trial that randomly assigned heifers into 1 of 4 different treatments: Control, vaccine 1 (bacterin and subunit proteins), vaccine 2 (bacterin), and vaccine 3 (recombinant subunit proteins).…”

“…It was a clinical trial that randomly assigned heifers into 1 of 4 different treatments: Control, vaccine 1 (bacterin and subunit proteins), vaccine 2 (bacterin), and vaccine 3 (recombinant subunit proteins). Heifers were immunized with a subcutaneous injection of its respective treatment at 240 ± 3 and 270 ± 3 d of gestation ( Meira Jr. et al., 2020 ). All vaccines were prepared by Merck Animal Health (DeSoto, Kansas, USA).…”

“…Immunization for metritis decreased incidence of puerperal metritis when compared with control (9.1% vs. 14.9%, respectively), and vaccine 3 alone reduced the incidence of puerperal metritis when compared with the control (8.0% vs. 14.9%, respectively) ( Figure 3 E). Immunization, especially with vaccine 3, improved reproductive performance ( Meira Jr. et al., 2020 ). Vaccination against metritis pathogens decreased the total vaginal bacterial load and decreased the vaginal load of F. necrophorum at nine days in milk.…”

“…The vaccine development efforts presented in studies 1 and 3 ( Machado et al., 2014 ; Meira Jr. et al., 2020 ) are going to become available for dairy producers soon and likely can be an instrumental tool to reduce the metritis burden and antimicrobials use. Considering, the insights of the ever-evolving field of uterine microbiome, it is reasonable to surmise that novel vaccines for metritis will be developed in the next decade to diversify the portfolio of tools to help mitigate the inherited cascade of adverse effects caused by metritis.…”