Development of a subcutaneous ear implant to deliver an anaplasmosis vaccine to dairy steers

Abstract

Bovine anaplasmosis is the most prevalent tick-transmitted disease of cattle worldwide and a major obstacle to profitable beef production. Use of chlortetracycline-medicated feed to control active anaplasmosis infections during the vector season has raised concerns about the potential emergence of antimicrobial resistance in bacteria that may pose a risk to human health. Furthermore, the absence of effectiveness data for a commercially available, conditionally licensed anaplasmosis vaccine is a major impediment to implementing anaplasmosis control programs. The primary objective of this study was to develop a single-dose vaccine delivery platform to produce long-lasting protective immunity against anaplasmosis infections. Twelve Holstein steers, aged 11 to 12 wk, were administered a novel 3-stage, single-dose vaccine against Anaplasma marginale, a major surface protein 1a. The vaccine consisted of a soluble vaccine administered subcutaneously (s.c.) for immune priming, a vaccine depot of a biodegradable polyanhydride rod with intermediate slow release of the vaccine for boosting immune response, and an immune-isolated vaccine platform for extended antigen release (VPEAR implant) deposited s.c. in the ear. Six calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing a combination of 2 different adjuvants, diethylaminoethyl (DEAE)-Dextran and Quil-A (Group A). The remaining 6 calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing the same adjuvant (either DEAE-Dextran or Quil A) (Group B). Twenty-one months post-implantation, calves were challenged intravenously with A. marginale stabilate and were monitored weekly for signs of fever, decreased packed cell volume (PCV) and bacteremia. Data were analyzed using a mixed-effects model and chi-squared tests (SAS v9.04.01, SAS Institute, Cary, NC). Calves in Group A had higher PCV than calves in Group B (P = 0.006) at day 35 post-infection. Calves in Group A were less likely to require antibiotic intervention compared with calves in Group B (P = 0.014). Results indicate that calves exhibited diminished clinical signs of anaplasmosis when antigen was delivered with a combination of adjuvants as opposed to a single adjuvant. This demonstrates the feasibility of providing long-lasting protection against clinical bovine anaplasmosis infections using a subcutaneous ear implant vaccine construct.

Bovine Anaplasmosis: Diagnosis, Treatment and Control Strategies

“…Proteins that in their native form have induce solid immunity have failed to induce immunity as recombinant counterparts (Sarli et al 2020) and even in some cases, animals inoculated with them showed worse clinical syndromes (Ducken et al 2015). An ear implant was designed to deliver Msp1a tandem repeat K;S as the antigen in a scheme that comprised three vaccination doses (prime-boost like) (Curtis et al 2020). As mentioned before, live organisms would seem to induce complete immunity against homologous and heterologous challenge.…”

Failure to Eliminate Persistent Anaplasma marginale Infection from Cattle Using Labeled Doses of Chlortetracycline and Oxytetracycline Antimicrobials

“…All steers were confirmed persistently infected with Am by PCR prior to study enrollment. Steers had been experimentally infected with a field isolate of Am (Msp1a genotype M-F-F, sourced from a naturally infected Am carrier cow in Oklahoma in 2018) approximately 120 days prior to onset of this clearance study [27]. The M-F-F strain is a naturally circulating field isolate that has not been previously evaluated for antimicrobial sensitivity.…”

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

“…A. marginale MSP1a was administered subcutaneously as priming, while a bio-erodible polyanhydride rod with intermediate slow release was used for boosting and the ear implant deposited subcutaneously was used to release antigen for a long time. The subcutaneous construct induced a durable protection against the pathogen, in particular when multiple adjuvants were used for antigen delivery [ 25 ].…”