30 May,2021 06:58 AM IST | Mumbai | Anju Maskeri
Three gorillas at San Diego Zoo, six bonobos and three orangutans were given the COVID-19 vaccine after a January 2021 infection at its safari park affected eight western lowland gorillas, the world’s first non-human primates to test positive
At Hyderabad's sprawling Nehru Zoological Park, Saina and Bahubali, two of the eight Asiatic lions who tested positive for the SARS CoV-2 virus last month, are slowly returning to their former perky selves. "We are once again seeing glimpses of their everyday personalities. All eight are, in fact, doing much better," says Siddhanand Kukrety, zoo director and curator. Not very different from humans infected with the virus, the big cats too had lost their appetite and were dull and lethargic. It was in late April, when the zookeepers noticed a nasal discharge in the lions housed in the Lion Safari Enclosures. The samples were sent to the Centre for Cellular and Molecular Biology (CCMB) in Hyderabad. It was a nervous time because this became only the second zoo in the world in 2020 after New York's Bronx Zoo, to have its animals test positive for the virus. The Wildlife Conservation Society that runs the NYC facility said in a statement that a four-year-old Malayan tiger named Nadia along with her sister Azul, two Amur tigers and three African lions all developed dry cough.
With the scientific world in a better position after a year of living with the pandemic to negotiate it, veterinarians and zoo staff the world over are considering giving a vaccine to animals that may be susceptible to the infection. Russia, in fact, has rolled out what it calls the world's first animal-specific jab, Carnivac-Cov, after trials showed that it generates antibodies in dogs, cats, foxes and mink. Six bonobos, four orangutans, and three gorillas at San Diego Zoo have also got the jab. Among them is Karen, the first orangutan to have had an open heart surgery in 1994.
In India, the Bareilly-based Indian Veterinary Research Institute (IVRI) is working to develop a vaccine, diagnostic kits and other tools to study the transmission dynamics of the Coronavirus in domestic pets and wild animals. "Trials and projects are on, but the results will be out in two years' time. Thankfully, the situation among animals is not alarming at this point. The big cats that got infected had mild respiratory symptoms, but they recovered well with treatment," says Dr KP Singh, acting joint director, Centre for Animal Disease Research and Diagnosis (CADRAD), ICAR-Indian Veterinary Research Institute. "We already have a vaccine for the Coronavirus that's found in poultry." The first Coronavirus ever discovered, back in the 1930s, was the avian Coronavirus known as Infectious Bronchitis Virus, or IBV. It is said to be the most infectious agent in hens.
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The Covid-19 vaccine that the San Diego Zoo used on its apes was produced by New Jersey-based Zoetis, the world's leading animal health company. Vaccines are among the products they develop for eight core species of animals: cattle, pig, poultry, sheep, fish, horse, cat and dog. According to Mahesh Kumar, senior vice president of global biologics at Zoetis, all vaccines developed for Covid-19 are not the same, including those administered to humans. "They use different technologies. However, all [vaccines] aim to induce an immune response against the virus. In our vaccine for animals, the vaccine antigen [the part that induces an immune response] is of the spike trimer combined with an adjuvant [an added carrier that boosts the immune response]. The adjuvant is the key differentiator in vaccines among the different species. While the antigen can be the same, the adjuvants are species-specific from a safety and efficacy standpoint." Zoetis has a long history of developing vaccines for other viruses from the Coronavirus family, for dogs, cats and farm animals, which is how Kumar explains, they were able to build on past experience when they started development activities for a new vaccine in February 2020, based on initial concerns about SARS-CoV-2 in domestic animals. "Thankfully, the disease has not become a significant issue in cats and dogs. However, our development work shifted to minks last year as they have been shown to be susceptible, and also a potential source of transmitting variant strains of the SARS-CoV-2 virus back to humans. Our goal in providing a vaccine for minks is to support what we call a "One Health" approach by helping protect them from the virus, which in turn helps protect human health."
Globally, besides the mink, the infection has been confirmed in dogs, domestic cats, tigers, lions, snow leopards, cougars and ferrets. Two canines in Hong Kong - a Pomeranian and a German shepherd - were reported to be the first domestic pets to contract the virus. Subsequently, other pets tested positive for the SARS-CoV-2 virus, including a cat in Hong Kong and another two in New York state. "Because many zoos are a point of contact between animals and humans, there is the potential of humans passing on the virus to the animals and vice versa. While the probability of these transmissions is low, it may be of concern," says Kumar.
During animal vaccine trials, they first test the safety of the vaccine, followed by its efficacy or degree of ability to fight the virus attack. "In this case, we vaccinate the animal and monitor its antibody response to see if there is a reasonable expectation of efficacy. Laws and regulations require us to study the species in question. We conduct many studies in vitro and then move on to host animals for pivotal safety and efficacy studies."
Dr Mohinder Oberoi is a Ludhiana-based virologist and former advisor to the Food and Agriculture Organisation of the United Nations (FAO). He says that traditionally there has been a close connection between viruses and animals. According to the Centres for Disease Control and Prevention, 75 per cent of all emerging infectious diseases come from animals. Covid-19 is thought to have originated in bats, who passed it on to humans in 2019. "Many specialist human viruses have mammalian or avian origins. But viruses such as Ebola, influenza and the Coronavirus are common to both species. They jump from animals to humans. While reverse transmission is not very common, it has reportedly happened in the case of Coronavirus. But studies show that the chances of it bouncing back from animals to humans is low."
It was 10 years ago that Rinderpest, also known as cattle plague, a highly contagious viral disease affecting cloven-hoofed animals (mainly cattle and buffalo) was officially declared as eradicated. Interestingly, it's the first and only animal disease to achieve this milestone. "It was eliminated with the help of vaccines, and encouragingly, the first vaccine [for rinderpest] was developed in India at the Indian Veterinary Research Institute, Mukteshwar. Vaccines can be highly effective in eradicating devastating viruses," says Dr Oberoi. The classic symptoms at the time were fever, erosive lesions in the mouth, discharge from the nose and eyes, profuse diarrhoea and dehydration, often leading to death within 10 to 15 days.
It was in late 2020 that SARS-CoV-2 jumped into the farmed mink in Denmark, where experts say it acquired mutations that were uncommon in humans. Dr Oberoi says virus mutations don't occur easily, even in animals. "[Birth of] mutant strains is common in many viruses, particularly in the ones that have RNA [ribonucleic acid] as its genetic material. Coronavirus and influenza both have RNA, so changes keep on occurring." While antigenic shift happens when two or more different strains of a virus combine to form a new subtype, antigen drift is a slow genetic variation in viruses, which happens continually over time as the virus replicates. "All of this doesn't happen overnight. It takes years and years, before it is noticed. We don't quite know for how long the Coronavirus has been present in bats or pangolins, where some theories claim it originated."
Meanwhile, national parks and zoos in India are pulling out all stops to ensure their animals are safe. Dr Kukrety, too, has strengthened security measures at their facility. "We suspect three reasons for how our lions got infected; one of our zookeepers, who was asymptomatic and twice tested negative, could have transmitted it. Second, it could have been transmitted via air. The third likelihood is that it could have come from the feed, but that's something we strictly monitor. Like everybody else, I think we let our guard down during the lean period when cases were on the decline."
Maharashtra's Additional Principal Chief Conservator of Forest, Sunil Limaye, says they have created a bio security bubble, where nobody apart from the keepers are allowed in the forest area. "After the casualty at Bronx Zoo, a central advisory was issued to monitor the health of animals in captivity; [to check] signs of panting, nasal discharge or fatigue. We have been keeping a close watch on the panthers, tigers and lions. The security guards in the wild have been trained and camera traps have been placed at strategic locations. " Senior principal scientist at CCMB, Karthikeyan Vasudevan, explains that unlike humans, it's not easy to collect swabs from wild animals in captivity. "We are trying to develop methods to detect the virus from fecal samples. We have to follow all biosafety norms strictly. This means that the workforce has to be trained and the facilities need an upgrade." When it comes to vaccines, he says all candidate vaccines are tested and pre-clinical trials are done before they can be approved by regulatory bodies and administered to animals. The National Institute of High Security Animal Diseases (NIHSAD) of Indian Council of Agricultural Research is the premier institute in India for research on emerging pathogens in animals. "Vaccines with a good report card should be efficacious. Others have to be viewed with caution."
75 per cent
Percentage of emerging infectious diseases that come from animals, according to Centres for Disease Control and Prevention
Last year, a team led by India-born virologist and professor SS Vasan, who has been leading the Covid-19 research at Australia's national science agency CSIRO (The Commonwealth Scientific and Industrial Research Organisation) established an animal model - the ferret - as a preclinical model to test Covid-19 vaccines and therapies. "While we have not tested any Covid-19 vaccines meant for animals, we have tested two different vaccines meant for humans in ferrets. One of them was Inovio's DNA vaccine. All human Covid-19 vaccines go through phased clinical trials - including a preclinical trial [tested in an animal model] and three human clinical trials. In the case of the preclinical trials conducted by Commonwealth Scientific and Industrial Research Organisation, it is the same vaccine; only the dose will be adjusted by the vaccine developer to reflect the weight of the animal," professor Vasan told mid-day in an email interview. Ferrets, it turns out, are a popular model for influenza and other respiratory infections because their lung physiology is similar to that of humans, and researchers hope they will mimic aspects of Covid-19 in people, including its spread.
Nasal discharge
Dry cough
Lethargy
Loss of appetite
