Anti-tick vaccines: A potential tool for control of the blacklegged ticks and other ticks feeding on whitetailed deer

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1 Anti-tick vaccines: A potential tool for control of the blacklegged ticks and other ticks feeding on whitetailed deer Andrew Y. Li USDA-ARS Invasive Insect Biocontrol and Behavior Laboratory (IIBBL) Beltsville, MD Integrated Tick Management Symposium: Solving America s Tick-Borne Disease Problem May 16-17, 2016 Washington, D.C.

2 Life cycle of Ixodes scapularis Tick control measurers: Dr. Rich Gary, Ohio Department of Health Area spray of pesticides: synthetic- versus bio-pesticides Host-targeted control (immature ticks): Tick tube, Bait box Host-targeted control (adult ticks): 4-Poster deer feeder Anti-tick vaccines for use on host animals (deer, mice)

3 Commercial Anti-tick vaccines: TickGARD (Australia) Gavac (Cuba) Both use recombinant Bm86 tick protein. Registration / commercialization in Australia and Latin American countries Continued field use in the following decade. Dr. Peter Willadsen Cattle tick Boophilus microplus Dr. Manuel Rodriguez Valle Dr. Jose de la Fuente

4 How does Bm86 work? Bm86 is a glycoprotein associated with midgut of the cattle tick, Rhipicephalus (Boophilus) microplus. Immunization of cattle with the recombinant Bm86 protein triggers immune response of cattle. Antibody-antigen interaction in the midgut lumen of feeding ticks causes damage to midgut membrane, leading to tick mortality, reduced female size, and reduced fecundity (# eggs laid, egg hatching rate). Cuba ( ) Use of GAVAC led to 87% reduction in number of acaricide use. de la Fuente & Kocan, 2014

5 Benefits of using Anti-tick vaccines: Mexico introduced in The number of acaricide applications was reduced from 24 to 7-8 / year (67% reduction). - More use of GAVAC to help acaricide resistance issues Tick Free R. annulatus R. microplus Veracruz, Mexico

6 Efficacy evaluation of the Bm86-based anti-tick vaccine Gavac against Texas outbreak strains of Rhipicephalus microplus and R. annulatus (Miller et al. 2012) Efficacy of Gavac against cattle fever ticks in Texas: - R. annulatus: 99.9% - R. microplus: 30%

7 Integrated strategy for sustainable cattle fever tick eradication: Possibility of use of anti-tick vaccine as a component of integrated cattle fever tick eradication. In 2016, Texas Animal Health Commission amended its roles to include use of fever tick vaccine in quarantine areas.

8 Other tick antigens: Antigen Tick species Reference Bm86 tick gut protein Rhipicephalus microplus Willadsen et al. (1988) BA86 tick gut protein Rhipicephalus annulatus Canales et al. (2008) Bm96 homolog of Bm86 Rhipicephalus microplus García-García et al. (2000) de la Fuente and Kocan (2003) HAA86 ortholog of Bm86 Hyalomma anatolicum anatolicum Azhahianambi et al. (2009) Jeyabal et al. (2010) 64TRP, Salp15 tick salivary proteins Ixodes scapularis Anguita et al. (2002) Salp25D, thrf Ixodes ricius Trimnell et al. (2002) TSLPI Dai et al. (2001, 2010) Schuijt et al. (2011) 64P cement protein Rhipicephalus appendicultus Trimnell et al. (2002) Ferritins iron-storage protein in Ixodes ricinus Kopacek et al. (2003) gut secreted into Hajduse et al. (2009) hemolymph Subolesin ortholog of insect akirins Ixodes scapularis Amazan et al. (2003, 2005) Aquoporin water channel protein Rhipicephalus microplus Guerrero et al. (2014)

9 Subolesin Subolesin was discovered as a tick protective antigen in a mouse model of the blacklegged tick I. scapularis (Almazan et al., 2003; 2005a,b). Subolesin is the ortholog protein of insect akirin (AKR) that has a broad function in transcription, immunity, gene expression, development and physiology (de la Fuente et al., 2006, 2011, 2015). Recombinant protein was expressed in E. coli, and was used to vaccinated mice, rabbit and sheep against infestation of larvae, nymphs and adults of I. scapularis. Results of vaccination with recombinant subolesin on different development stages of I. scapularis. Stage Host Effects Larva mouse Reducing molting to nymphs by 71% nymph rabbit Reducing #of engorged engorged nymphs by 35% adult rabbit immune sera Caused 25% mortality (capillary feeding) Reduce weight gain by 35% PAGE of recombinant 4D8 protein (Subolesin) D. Variabilis nymphes fed on 4D8-vaccinated rabbit. Also effective against other tick species, including: - American dog tick, D. Variabilisis - Lone star tick, A. americanum - Rhipicephalus spp. Almazan et al Vaccine 23: De la Fuente et al Transbound Emerg. Dis. 60:

10 Discovery of aquaporin gene in R. microplus. cdna expression of RmAQP1 in Pichia pastoris to produce the recombinant protein. Cattle vaccination trials in Brazil

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13 Vaccination of livestock versus wildlife Livestock cattle, sheep, etc. Subcutaneous injection Intra-nasal administration Oral vaccine cattlebreeders.org Wildlife such as whitetailed deer Needle injection? Dart gun Oral vaccine Oral Rabbies Vaccine GonaCon Birth Control for Deer Humane Society of the United States

14 USDA -ARS National Animal Disease Center Ames, IA USDA-APHIS National Wildlife Center Fort Collins, CO Oral Vaccine of white-tailed deer with Mycobacterium bovis Bacillus Calmette-Guerin (BCG) to prevent the transmission of bovine tuberculosis to other deer and cattle

15 Cattle Tick Vaccine Consortium (CATVAC) Working pipeline proposed by CATVAC for development of effective vaccines for cattle tick control A meeting sponsored by the Bill & Melinda Gates Foundation was held at the Avanti Hotel, Mohammedia, Morocco. July 14 15, The meeting resulted in the formation of the Cattle Tick Vaccine Consortium (CATVAC).

16 European approach toward solving ticks and tick-borne disease affecting humans, animals and wildlife ANTIDotE: ANti-tick vaccines to prevent TIck-borne Diseases in Europe Ixodes ricinus Sprong et al Parasites & Vectors 7:77.

17 Sprong et al Parasites & Vectors 7:77. Call to form a similar Anti-tick Vaccine Consortium in the U.S. Collaboration among researchers to facilitate research progress. Government, university, industry entities and non-profit organizations. Focusing on tick species and pathogens affecting human health. Existing and new antigens. in vitro and in vivo efficacy trials. Oral formulations for wildlife (whitetailed deer & whitefooted mouse) Funding for the work: - Industry? - Private foundations / Nonprofit organizations? - Government agencies?

18 Summary Two commercial anti-tick vaccines have been successfully developed to control cattle ticks. The Bm86-based vaccine can achieve near 100% efficacy against R. annulatus ticks. There are a number of promising anti-tick antigens that have been evaluated against several different tick species, including I. scapularis, resulting in 60-70% efficacy. Anti-tick vaccines can potentially be a useful tool for Integrated Tick Management for control of blacklegged ticks on deer and rodents. Many challenges exist for development of such vaccine products. Call for forming a anti-tick research group in the U.S. to facilitate novel antigen discovery and product development. Funding for anti-tick vaccine research by federal government is required in order to make substantial progress toward anti-tick vaccine products that can help control ticks and reduce the risk of tick-borne diseases, particularly Lyme disease.

19 Acknowledgments USDA-ARS-KBUSLIRL Felix Guerrero Adalberto Perez de Leon USDA-ARS Area-wide Pest Management program USDA-NIFA Northeast IPM Center Beltsville Agricultural Center