Anti-tick vaccines: A potential tool

for control of the blacklegged ticks and other ticks

feeding on whitetailed deer

USDA-ARS

Invasive Insect Biocontrol and Behavior Laboratory (IIBBL)

Beltsville, MD

Andrew Y. Li

Integrated Tick Management Symposium:

Solving America’s Tick-Borne Disease Problem

May 16-17, 2016

Washington, D.C.

Agricultural

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Service

Life cycle of Ixodes scapularis

Tick control measurers:

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)

Dr. Rich Gary, Ohio Department of Health

http://wildlife.ohiodnr.gov/species-and-habitats/ticks-in-ohio

Agricultural

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Commercial

Anti-tick vaccines:

TickGARD (Australia)

Gavac (Cuba)

Both use recombinant Bm86 tick protein.

Registration / commercialization in

Australia and Latin American countries

1993-1997.

Continued field use in the following

decade.

Dr. Manuel

Rodriguez Valle

Dr. Peter Willadsen

Dr. Jose de la

Fuente

Cattle tickBoophilus microplus

Agricultural

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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).

de la Fuente & Kocan, 2014

Cuba (1995-2003)

Use of GAVAC led to 87%

reduction in number of

acaricide use.

Agricultural

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Benefits of using Anti-tick vaccines:

Veracruz, Mexico

Tick FreeR. annulatusR. microplus

Mexico – introduced in 1997

- The number of acaricide applications was reduced

from 24 to 7-8 / year (67% reduction).

- More use of GAVAC to help acaricide resistance

issues

Agricultural

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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%

Agricultural

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Possibility of use of anti-tick vaccine as a component

of integrated cattle fever tick eradication.

Integrated strategy for

sustainable cattle fever tick eradication:

In 2016, Texas Animal Health Commission amended its

roles to include use of fever tick vaccine in quarantine areas.

Agricultural

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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)

Other tick antigens:

Agricultural

Research

Service 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.

PAGE of recombinant 4D8

protein (Subolesin)

D. Variabilis nymphes fed

on 4D8-vaccinated rabbit.

Almazan et al. 2005. Vaccine 23: 4403-4416.

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%

Also effective against other tick species, including:

- American dog tick, D. Variabilisis

- Lone star tick, A. americanum

- Rhipicephalus spp.

De la Fuente et al. 2013. Transbound Emerg. Dis.

60: 172-178.

Agricultural

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Discovery of aquaporin gene in R. microplus.

cDNA expression of RmAQP1 in Pichia pastoris

to produce the recombinant protein.

Cattle vaccination trials in Brazil

Agricultural

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Agricultural

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Agricultural

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Vaccination of livestock versus wildlife

Livestock – cattle, sheep, etc.

Subcutaneous injection

Intra-nasal administration

Oral vaccine

Wildlife – such as whitetailed deer

Needle injection?

Dart gun

Oral vaccine

cattlebreeders.org

GonaCon™ Birth

Control for Deer

Humane Society of the United States

http://www.usatoday.com/

Oral Rabbies Vaccine

Agricultural

Research

Service

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

USDA -ARS

National Animal Disease Center

Ames, IA

USDA-APHIS

National Wildlife Research Center

Fort Collins, CO

Agricultural

Research

Service

Working pipeline proposed by CATVAC

for development of effective vaccines

for cattle tick control

Cattle Tick Vaccine

Consortium (CATVAC)

A meeting sponsored by the Bill &

Melinda Gates Foundation was held at

the Avanti Hotel, Mohammedia,

Morocco. July 14–15, 2015.

The meeting resulted in the formation

of the Cattle Tick Vaccine Consortium

(CATVAC).

Agricultural

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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. 2014. Parasites & Vectors 7:77.

Agricultural

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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 ?

Sprong et al. 2014. Parasites & Vectors 7:77.

Agricultural

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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.

Summary

Agricultural

Research

Service

USDA-ARS-KBUSLIRLFelix Guerrero

Adalberto Perez de Leon

USDA-ARSArea-wide Pest Management

program

USDA-NIFANortheast IPM Center

Acknowledgments

Beltsville Agricultural Research Center