Harvard animal studies suggest COVID-19 protection can come from previous infection or DNA vaccine

Syringe injection vaccine needle
DNA and mRNA vaccines to fight COVID-19 are racing through development, though scientists are raising questions about the durability of the neutralizing antibodies they generate. (Pixabay)

In all the excitement over the potential for a quick vaccine to prevent COVID-19, one burning question has emerged: Are the antibodies that form in response to the virus adequate for fending off future infections? Scientists led by Harvard University have published two studies that they believe begin to answer that question.

In one study, nine macaques that were infected with SARS-CoV-2 and then recovered were protected against the disease when they were exposed to it again 35 days later. The team showed the animals had developed neutralizing antibodies, which prevent the virus from infecting healthy cells. In separate research, 35 macaques received DNA vaccines developed at Harvard and showed similar immune responses as the animals involved in the first study did. The papers were published in the journal Science.

People who recover from many viruses typically form antibodies that protect them against future infections—but not always, the Harvard team pointed out in one of the studies. And COVID-19 is so new that no one knows to what degree people who have antibodies against the disease are protected.

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“This is a critical issue with profound implications for vaccine development, public health strategies, antibody-based therapeutics, and epidemiologic modeling of herd immunity,” the authors wrote in the study involving macaque models of COVID-19 infection.

In that study, the Harvard team infected the monkeys with SARS-CoV-2 and then measured the viral load in the bronchial tract and nasal passages. All of the animals became mildly ill, showing some loss of appetite but no fever or respiratory distress, the researchers reported. All nine monkeys had similar levels of neutralizing antibodies 35 days later, even though some had been given higher doses of the virus than others.

Could DNA vaccines also generate protective antibodies against COVID-19? That’s the idea behind INO-4800, a DNA vaccine being sped through development by Inovio Pharmaceuticals. The vaccine works by delivering plasmid DNA into cells, which then generate antigens to prompt an immune response. The company announced Thursday that in preclinical models, INO-4800 generated neutralizing antibodies—and that they used three different assays to confirm it. Furthermore, the company said in a statement, the studies showed that the vaccine generated “high levels” of T cells specific to the spike protein on the surface of SARS-CoV-2.

T-cell responses have become a major topic of conversation, not only for Inovio but also for Moderna, which is rapidly developing an mRNA vaccine against COVID-19. That’s because T-cell responses are considered an important indicator that the immune system is defeating the virus. Moderna’s shares rose nearly 30% Monday on positive early data from human and animal trials, though some analysts griped that the company didn’t provide enough details about T-cell responses in the patients who responded well to the mRNA vaccine.

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Inovio has generated its fair share of controversy, as well. The company’s shares more than doubled to $15 in April, spurred on, no doubt, by a “60 Minutes” feature in which the company’s senior vice president of R&D, Kate Broderick, said the company was able to design INO-4800 in three hours. That led critic Citron Research to call Inovio’s management team “charlatans” and to remind investors that the 40-year-old company has yet to release a product.

Harvard scientists wanted to test the DNA vaccination concept themselves, so a team led by the university’s Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center constructed a series of vaccines expressing six variants of the SARS-CoV-2 spike protein. They tested them in 25 macaques and gave an additional 10 animals a placebo.

All of the monkeys were then exposed to the virus, after which the researchers compared their levels of neutralizing antibodies with those found in the infected macaques from the other Harvard study, as well as those from people who suffered COVID-19 and recovered. The levels of neutralizing antibodies in the animals that received the DNA vaccines were comparable, they reported.

All of this is encouraging given how rapidly DNA and mRNA vaccine development is moving, to be sure. But even the Harvard researchers acknowledged the jury is still out on the potential value of vaccination against COVID-19. “Further research will need to address the important questions of the durability of protective immunity and the optimal vaccine platforms for a SARS-CoV-2 vaccine for humans,” wrote the authors of the DNA vaccine study.

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