More than Three Decades of Bm86: What We Know and Where to Go

Abstract

Tick and tick-borne disease control have been a serious research focus for many decades. In a global climate of increasing acaricide resistance, host immunity against tick infestation has become a much-needed complementary strategy to common chemical control. From the earliest acquired resistance studies in small animal models to proof of concept in large production animals, it was the isolation, characterization, and final recombinant protein production of the midgut antigen Bm86 from the Australian cattle tick strain of Rhipicephalus (Boophilus) microplus (later reinstated as R. (B.) australis) that established tick subunit vaccines as a viable alternative in tick and tick-borne disease control. In the past 37 years, this antigen has spawned numerous tick subunit vaccines (either Bm86-based or novel), and though we are still describing its molecular structure and function, this antigen remains the gold standard for all tick vaccines. In this paper, advances in tick vaccine development over the past three decades are discussed alongside the development of biotechnology, where existing gaps and future directives in the field are highlighted.

Evolution of tick vaccinology

“…To improve vaccine efficacy, posttranslational modifications such as alpha-gal have also been considered to improve vaccine efficacy (Hodžić et al, 2020). Moreover, characterization of tick-host-pathogen interactions, immune protective and acaricide-resistance mechanisms (Bhowmick and Han, 2020;Bishop et al, 2023;Waldman et al, 2023), transgenesis and paratransgenesis for the genetic manipulation of commensal bacteria and ticks (Sharma et al, 2022;Mazuecos et al 2023a;de la Fuente et al, 2023b) and combination of vaccines with other interventions such as natural plant and animal-derived compounds and cultural practices among other interventions (Showler and Saelao, 2022) were considered as possible alternatives. International collaborations with regions with high incidence of tick infestations and TBD (Estrada-Peña and de la Fuente, 2023), personalized medicine approach based on regional, tick species/strains and host-driven variables (Kasaija et al, 2020) are also proposed for sustainable management of the relevant vector.…”

“…Ticks are difficult to control, and traditional control methods are mainly based on the use of chemical acaricides with partial success and drawbacks such as selection of resistant ticks and negative impact on animal health and production and environmental contamination (Agwunobi et al, 2021;Githaka et al, 2022;Gonzaga et al, 2023). A number of reports of establishment of multiacaricides resistant ticks in different parts of the world (Bishop et al, 2023) and growing global public concern of environment pollution due to high use of chemical acaricides has posed serious challenges on continuation the use of conventional methods for tick management.…”

“…Under the One Health and sustainability perspective, vaccines are the most effective and safe intervention to reduce tick populations and risks associated with transmitted pathogens (de la Fuente, 2018;reviewed by Estrada-Peña et al, 2022). However, although a number of reports of significant efficacy of other vaccine formulations have been reported (de la Fuente and Kocan, 2003;de la Fuente and Contreras, 2015;Bishop et al, 2023;Parizi et al, 2023), only Bm86/Bm95-based vaccines TickGARD in Australia and Gavac in Cuba were registered and commercialized for the control of Rhipicephalus microplus tick infestations (de la Fuente et al, 2007;Rodríguez-Mallon, 2023). Currently, only Gavac (CIGB, Havana, Cuba; https://www.cigb.edu.cu/en/product/gavac-2/) and Bovimune Ixovac (Lapisa, La Piedad, Michoacán, Mexico; https://lapisa.com/productos/bovimune-ixovac) with Bm86 antigen are still commercially available in some Latin American countries.…”

Genetic Diversity of Rhipicephalus (Boophilus) microplus for a Global Scenario: A Comprehensive Review

“…Non-coding loci are frequently utilized in phylogenetic investigations for species differentiation, including the internal transcribed spacer regions (ITS-1 and ITS-2) and the 18S and 28S ribosomal genes [ 24 , 38 , 45 , 46 ]. In a previous study, Zahler et al [ 47 ] utilized a 274base pair segment of the ITS-2 sequence to establish the conspecific nature of six closely related tick species within the R. sanguineus complex.…”

“…Moreover, genetic diversity in protein coding genes, Bm86, a vaccine candidate against R. microplus and synthetic pyrethroid resistance-conferring genes, and sodium channels are also included here. Bm86-based commercial vaccines are available underthe trade names of TickGARD ® (Hoechst, Australia), TickGARD PLUS ® (Intervet, Australia), and Gavac ® (Heber Biotec, Havana, Cuba) [ 37 , 38 ]. However, the efficacy of commercial vaccines varies across geographical areas [ 39 , 40 , 41 , 42 ] due to variations and polymorphism in the Bm86 gene, and this is one of the major impediments to its commercializing globally as an anti- R. microplus vaccine.…”