On 18 August 2021, Joe Biden, the president of the United States of America, announced that people who had received the Pfizer and Moderna vaccines for COVID-19 would need a third dose eight months after their second doses. He later updated it to a five-month gap between the second and third doses. Israel, one of the countries with the highest vaccination coverage, is now preparing for a fourth dose of vaccines for its population. Meanwhile, India has hastily approved a DNA vaccine without fully considering possible long-term consequences.
The world over, governments have hurriedly given emergency-use authorisation for COVID-19 vaccines, relying on the preliminary data of efficacy from phase III trials. The duration of protection offered by vaccines and the catalogue of serious adverse effects will be known only after two years, once all the data from the phase III trials is available. In India, we have gone one step further and have permitted the use of vaccines with no published phase III data. This is unnecessarily risky.
Biden’s decisions about the booster doses seem to have been announced in panic, even before the US Food and Drug Administration had evaluated the need for the extra dose. Ostensibly, this decision was taken to stymie the spread of the highly contagious Delta variant of the novel coronavirus. Rochelle Walensky, the director of the US Centers for Disease Control and Prevention, or CDC, was more forthcoming when she said in a press briefing that vaccine protection was waning. She said that data from Israel showed an increased risk of severe disease among those vaccinated early.
The severe disease in the vaccinated is reminiscent of what happened with a dengue vaccine a few years ago. Initially, Dengvaxia, which was made by Sanofi and launched in the Philippines in 2016, seemed to evoke a good antibody response in recipients. However, when exposed to the virus in the next dengue season, the vaccinated suffered more serious symptoms than the unvaccinated. This fiasco resulted in criminal charges against the vaccine makers in the Philippines.
The antibodies against viruses are of various types and generally act as protective agents. Most of the antibodies are usually what are called neutralising antibodies. However, some antibodies, called facilitating antibodies, paradoxically help the virus and make the condition of the patient more serious. Another type of antibodies, called binding antibodies, can cause further problems. Binding antibodies cannot eliminate the virus but they activate the “panic button” of the immune system. They stimulate cytokines in the body, which are proteins that act mediating agents in the growth and activity of cells in the immune system. If levels of neutralising antibodies fall, which they tend to do over time, the binding antibodies may cause unregulated production of such mediators and cause a cytokine storm that overwhelms the body, and result in multi-organ dysfunction and even death. The mechanism of such antibodies causing more severe disease is called antibody-dependent enhancement or ADE.