The Safety and Efficacy of the Ticvac Tick Vaccine Against Tick-Borne Diseases in Uganda

Prevention of infectious diseases in beef cattle through vaccination is critically important. Vaccines provide a safer, effective, and economically important immunologic prevention of infectious diseases that wreak havoc on animal welfare as well as threaten human populations that depend on beef and milk consumption.

One of the most effective methods of preventing infectious disease in cattle or humans is vaccination. Vaccines have played a critical role in preventing the global spread of covid among humans and will continue to do so. Due to the severe impact of the covid pandemic, vaccination programmes have become an integral part of many governments’ strategic initiatives to control both human and herd health. 
Vaccination of cattle in Uganda has been earmarked as a strategic imperative because of the importance of livestock to Uganda’s economy. The cost of treating tick-borne diseases in Uganda is astronomical.

Uganda loses more than US$1.1billion annually due to ticks and tick-borne diseases, spending over US$83.3million just on importing 378,000 litres of acaricides and 83,000 litres of associated drugs annually. This excludes the other effects of tick-borne diseases on mortality, loss in beef and milk production (US$659million) and other costs. 

Lowering the incidence of ticks and tick-borne diseases in Uganda through vaccination will thus have a profound impact not just on animal welfare but it will also provide considerable economic benefits to both cattle farmers and the country.

Further, vaccination is better than the use of chemical acaricides for food animals because vaccination of animals used for food consumption can also help protect consumers against zoonotic pathogens (those which can pass from animals to humans).

Vaccination doesn’t just stimulate effective and long-lasting immunity to infectious disease in animals but it can also help protect consumers against zoonotic pathogens that pass from animals to humans. COVID‐19 was a perfect example of a zoonotic—the virus causing it jumped from an animal to a human host.

This is why the development of TicVac-U, the first East Coast Fever vaccine in Uganda, has been aggressively supported by many stakeholders, including H.E the President of Uganda Yoweri K. Museveni as well as industry policy makers and national institutions including the National Drug Authority (NDA), Makerere University, COVAB, and many others.

It is the first tick vaccine developed in Uganda in an effort to address the challenge of ticks and tick-borne diseases affecting livestock in the country.

It was developed by Professor Margaret Saimo-Kahwa, in collaboration with scientists from MAK-COVAB, using vaccine candidate proteins from local ticks which have been exploited to produce an anti-tick vaccine that can effectively immunize local cattle to prevent East Coast Fever (ECF) and Babesiosis, the two most prevalent and economically important Tick-Borne Diseases affecting Uganda's cattle population. 

How do vaccines work?

Vaccines work in a fairly simple way. When any animal or a cow (in our case) picks up an infection, its immune system goes to work to try and fight the intruder pathogens. The immune system is the body’s natural defence against infection. However, sometimes, the animal’s immune system cannot respond quickly enough to avert the infection from seriously harming or even killing the animal. 
One way to give an animal’s immune system an edge in the fight against intruder pathogens, is to use a vaccine.

A vaccine in simple terms is a biological preparation, typically containing weakened or dead forms of pathogenic bacteria/virus toxins or some of the surface proteins (known as antigens). Once these weakened or dead antigen agents are introduced into the body via vaccination, they trick the animal’s immune system into recognizing the agents as threats, consequently developing a capacity to destroy such antigens.

However, this is not all. The immune system will store a ‘memory’ of the pathogens antigens so that the next time the animal picks up that infection or any closely related bacteria/virus toxin in the future, its immune system will quickly respond to either prevent or significantly reduce the harm to the animal. 

The ability of a vaccine to stimulate an immune response is what is referred to as immunogenicity (or the ability of living cells/tissues to provoke an immune response). It is a central aspect of effective and safe vaccine development, which is why TicVac-U has been developed to fulfil this key criterion.

Immunogenicity is a critical component of vaccine production all over the world. There are two ways of stimulating an immune response via vaccination – 
1) introduce disease-causing modified live viruses (MLV) or bacteria that have been weakened or ‘attenuated’ in a laboratory. This type of modified live viral vaccine provokes a satisfactory immune response with a single dose.
2) introduce dead or inactivated forms of the pathogen or their toxins, inactivated with heat, chemicals like formalin, or radiation. This type of vaccine works slower and the effect is usually temporary, with the number of antibodies produced decreasing over time, although additional doses later can ‘boost’ the response.

Both vaccine methods work effectively and the introduction of pathogens to stimulate an immune response is what makes vaccines the safest form of disease prevention.

Ticvac-U vaccine safety

One of the key benefits that makes Ticvac safe for cattle as well as beef or milk consumption from vaccinated animals is that it works on the same principle of immunogenicity discussed earlier. Ticvac-U is designed to stimulate an immune response in cattle. 

When Ticvac scientists were testing the candidate vaccine proteins during early laboratory clinical trials, the first thing the team wanted to see was if it induces an immune response in the body of the animals so they produce antibodies. The animals were able to do this successfully. This is critical as immunogenicity is a central aspect of effective and safe vaccine development across the world, a TicVac-U. 
This is why Ticvac, the first anti-tick vaccine developed in Uganda, has been approved by the National Drug Authority. It has been verified safe based on its zero effect not just on the health of vaccinated cattle but also the consumption of meat or milk from cattle vaccinated using Ticvac-U.

Ticvac scientists were able to achieve this by formulating a vaccine candidate that had tick proteins which could produce an immunogenic response to fight off ticks and consequently any tick-borne diseases.

According to Dr. Kokas Ikwap, the Principle Parasitologist of the Ticvac anti-tick vaccine production initiative, Ticvac has two components – a) an antigen protein (extracted from local Ugandan ticks which helps to stimulate an immune response and b) adjuvants (chemicals that increase the vaccine efficacy). 

Parasitologist Dr. Kokas Ikwap explaining the safety of Ticvac on vaccinated animals

The safety of the Ticvac vaccine was first tested on mice during laboratory clinical trials. The mice were injected with the candidate vaccine protein regularly to try and understand its effect on them and their internal organs.

The results from the laboratory trials revealed that Ticvac, which is also a tick vaccine for Babesiosis in Uganda, did not have any effect on the tested mice. Ticvac scientists did not observe any damage either to the tissues or the different organs of the mice during testing, implying that the candidate vaccine has no effect on the animal that has been vaccinated with Ticvac or the meat that’s consumed from vaccinated animals.

Furthermore, the antigen proteins extracted from the ticks and formulated into the Ticvac vaccine are broken down by the immunized cattle and within a few months, there is no tick protein left at all in the animals. This is because antigens are of a biological nature and thus are broken down rapidly in the body, sometimes in a matter of days – meaning an animal can be slaughtered and safely eaten immediately after vaccination. 

The result is that Uganda’s first tick vaccine, which is also the first vaccine for East Coast Fever as well as Babesiosos in Uganda, fulfils the immunogenic criteria of safe and effective vaccines due to its ability to stimulate an antibody response against tick-borne antigens. 

The efficacy of Ticvac-U against East Coast Fever and other tick-borne diseases in Uganda 

What is vaccine efficacy? How is it different from vaccine efficiency?
The distinction between vaccine efficacy and efficiency is critical for understanding vaccination management.

Efficacy of a vaccine refers to the percent reduction in disease incidence and pathology in a vaccinated group compared with an unvaccinated group.  A high vaccine efficacy means high biological activity and the ability of the vaccine to stimulate a strong active immune response against the agents in the vaccine. 

Vaccine efficiency on the other hand refers to the ability of a vaccine to improve health outcomes in the production setting.  In commercial cattle production, vaccine efficiency translates to a significant reduction in clinical illness and/or death loss, improvement in weight gain, and a clear economic advantage.  

In clinical trials against both East Coast Fever and Babesiosis (the two most prevalent and economically important Tick-Borne Diseases affecting Uganda), overall efficacy of the Ticvac vaccine was 86% for the R. appendiculatus vector- the brown ear adult ticks responsible for transmitting East Coast Fever (ECF). 
For R. decoloratus which is the most common tick species that transmit Babesiosis, TicVac-U efficacy was 53%.

IN SUMMARY

In summary, immunogenicity or the ability of a vaccine to stimulate natural immunity against disease is a critical aspect of effective and safe vaccine development.

Ticvac has been developed with immunogenicity as its core mechanism of working, as it uses tick proteins to help cattle develop the capacity to destroy disease carrying pathogens.

One of the biggest advantages of vaccination over the use of chemical acaricides in preventing diseases is the positive impact on both cattle and human welfare. Meat and dairy from animals vaccinated with the Ticvac vaccine is safe to consume because of the way it uses immunogenicity to disease prevention. Vaccines approved for use in food animals globally use the same principle.
 

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Dec 26, 2021