Oral Vaccination With a Formulation Combining Rhipicephalus microplus Subolesin With Heat Inactivated Mycobacterium bovis Reduces Tick Infestations in Cattle

Abstract

Vaccines are an environmentally friendly alternative to acaracides for the control of tick infestations, to reduce the risk for tick-borne diseases affecting human and animal health worldwide, and to improve animal welfare and production. Subolesin (SUB, also known as 4D8) is the functional homolog of Akirin2 involved in the regulation of development and innate immune response, and a proven protective antigen for the control of ectoparasite infestations and pathogen infection. Oral vaccination combining protein antigens with immunostimulants has proven efficacy with increased host welfare and safety, but has not been used for the control of tick infestations. Here we describe the efficacy of oral vaccination with a formulation combining Rhipicephalus microplus SUB and heat inactivated Mycobacterium bovis (IV) on cattle tick infestations and fertility. The levels of IgG antibody titers against SUB and M. bovis P22, and the expression of selected immune response genes were determined and analyzed as possible correlates of protection. We demonstrated that oral immunization with the SUB+IV formulation resulted in 51% reduction in the number of female ticks and 30% reduction in fertility with an overall efficacy of 65% in the control of R. microplus infestations by considering the cumulative effect on reducing tick survival and fertility in cattle. The akr2, IL-1 β, and C3 mRNA levels together with antibody levels against SUB correlated with vaccine efficacy. The effect of the oral immunization with SUB+IV in cattle on tick survival and fertility is essential to reduce tick infestations, and extended previous results on the effect of R. microplus SUB for the control of cattle tick infestations. These results support the development of oral vaccines formulations for the control of tick infestations and the incidence of tick-borne diseases.

Vaccination with Recombinant Subolesin Antigens Provides Cross-Tick Species Protection in Bos indicus and Crossbred Cattle in Uganda

“…Antibody response to vaccination with SUB has been shown to be the main protective mechanism against tick infestations [ 33 ], although cell-mediated immunity may play a role with certain vaccine formulations [ 34 ]. Anti-SUB antigen-specific IgG antibody titers were determined on each vaccinated and adjuvant-alone treated controls in sera collected before each vaccination (days 0, 30 and 60), at day 45 between second and third vaccinations and at the end of the experiment (days 180 or 195 for B. indicus and crossbred cattle, respectively) ( Figure 4 A,B).…”

“…Based on these evidences, we propose to use R. appendiculatus SUB to continue research on vaccine design and formulation. Future directions would include quantum vaccinology approaches based on the characterization of the SUB protective epitopes [ 32 ] and tick-pathogen interactions [ 47 ], modeling of the vaccine E under Ugandan ecological and epidemiological conditions [ 4 ] and optimization of vaccine formulation including the possibility of oral administration to improve cattle welfare and safety [ 34 ].…”

Towards a Multidisciplinary Approach to Improve Cattle Health and Production in Uganda

“…Other livestock, particularly sheep and goats, that are likely to be in contact with cattle should also be tested and it would be ideal to include wildlife too. Moreover, further opportunities emerge from the possibility of using heat-inactivated M. bovis as an immunostimulant in oral vaccination against ticks [27].…”

Towards an Effective, Rational and Sustainable Approach for the Control of Cattle Ticks in the Neotropics

“…Despite recent advances in the identification and characterization of tick protective antigens [52][53][54], the major challenges faced to further advance the implementation of effective vaccination strategies for the control of cattle tick infestations and tick-borne diseases include: (a) rational and effective combination of anti-tick vaccines with acaricides and other traditional control measures; (b) development and implementation of cost-effective and safe vaccines reducing infestations by multiple tick species in different hosts; (c) vaccine formulations to reduce tick infestations and pathogen infection and/or transmission; and (d) funding and fulfilling regulatory requirements for vaccine registration. To address these challenges we propose (a) to use information on tick life cycle and the effect of biotic and abiotic factors for the effective combination of multiple control measures including vaccines for the control of tick infestations and pathogen infection and transmission [55]; (b) modeling the vaccination strategies against ticks and transmitted pathogens to guide the selection of appropriate antigen combinations, target hosts and vaccination time schedule [53]; (c) to use latest omics technologies in a vaccinomics approach combined with systems biology and big data machine learning algorithms to identify new protective antigens and advance quantum immunology [56,57]; (d) to combine tick-derived and pathogen derived antigens in effective vaccine delivery formulations to target multiple tick species in domestic and both domestic and wild hosts [55][56][57][58]; (e) to develop country and host/tick species driven strategies to increase the efficacy of vaccination and other control strategies for cattle ticks and transmitted pathogens [59]. Finally, it is important to advance research on areas such as sequencing and assembly of tick genomes, vector competence, functionality of tick microbiota, functional analysis of tick-host-pathogen interactions, and pathogen control of tick/host epigenetics to develop vaccines and methods to manipulate tick genetics and microbiota for new effective interventions to control tick infestations and transmitted pathogens affecting both human and animal health [60,61].…”