Uncharted territory
While some support the idea of a mandate, others are skeptical and say it would infringe on personal freedoms.
Robert F. Kennedy, Jr. is an attorney and the president of the children’s Health Defense. He’s worried about how new the vaccine is and how complicated it is to get right.
“There’s a peculiar problem with the COVID vaccines that is almost unique,” Kennedy Jr. said.
He’s worried about the risk of antibody-mediated disease enhancement, which could cause a more serious reaction to coronaviruses by enhancing the disease rather than protecting against it.
ADE is considered to be rare and there is no proof that the phenomenon exists in COVID-19. However, Kennedy Jr. is worried about the possibility.
“I think it’s a healthy thing to question the pharmaceutical industry. I’m not anti-vaccine, although people call me anti-vaccine. I had all of my children vaccinated and if this vaccine says what people say it’s going to do, then I will take it, but we should be able to have a debate about that,” Kennedy Jr. said.
He believes the COVID-19 vaccine that is eventually approved will perform more like a flu vaccine and will require regular doses.
“I think that to be optimistic about getting a vaccine for the coronavirus that’s better than the flu vaccine is unlikely,” he said.
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For SARS and MERS, antibodies against the viruses – elicited either by infection or vaccination – have been shown to cause ADE in animal models, including non-human primates. In cell cultures, they have been shown to potentiate infection of primary human macrophages.
There’s also evidence that feline infectious peritonitis virus, a coronavirus that infects domestic cats, is enhanced both by maternal antibodies transferred to kittens and by vaccination, resulting in severe and fatal feline disease.
Halstead is unaware of any “evidence that severe or fatal SARS or MERS result from antibody-mediated infections.”
Vaccine developers “must be aware of and look for” the possibility of ADE caused by COVID-19 vaccines, he cautioned.
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https://www.pnas.org/content/117/15/8218
Rogue Responses
Graham emphasizes alternative ways in which a vaccine could potentially induce more serious COVID-19 infections: Th2 immunopathology, in which a faulty T cell response triggers allergic inflammation, and poorly functional antibodies that form immune complexes, activating the complement system and potentially damaging the airways.
Both processes were at play as an unfortunate situation unfolded in the 1960s, according to Graham. Researchers at the time were pursuing a vaccine against RSV, the leading cause of severe respiratory illness in infants. In trials of one vaccine candidate, several children who received the vaccine developed a serious illness when infected with the natural virus (7). Two toddlers died. In this case, researchers noticed severe damage and the unexpected presence of lots of neutrophils and eosinophils, both immune cells, in the children’s lung tissue. A similar inflammatory response was seen in animal models of RSV, in which cytokines, a type of immune cell, had invaded and damaged tissue.
“That really killed RSV vaccines for a generation,” says Peter Hotez, a vaccine researcher and dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, TX. After more than 50 years of further study, a candidate RSV vaccine is finally back in clinical trials.
When SARS, also a coronavirus, appeared in China and spread globally nearly two decades ago, Hotez was among researchers who began investigating a potential vaccine. In early tests of his candidate, he witnessed how immune cells of vaccinated animals attacked lung tissue, in much the same way that the RSV vaccine had resulted in immune cells attacking kids’ lungs. “I thought, ‘Oh crap,’” he recalls, noting his initial fear that a safe vaccine may again not be possible.
But his team revised their approach. Instead of producing the whole spike protein of the virus, they built just a tiny piece of it—the piece that attaches to human cells, called the receptor-binding domain. Subsequent animal tests showed that this strategy did provide the desired protection without the unwanted immune enhancement. With funding from the NIH, Hotez’s team continued on to manufacture the vaccine and were ready for clinical trials.
[DON’T SKIP “confirmatory testing against SARS-CoV challenge in animal models”]
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