Need for speed in Covid-19 vaccine creates challenges and enhancement danger

The world needs a Covid-19 vaccine and assurances that it will be safe

  • There are at least 149 projects underway to develop a Covid-19 vaccine and many of these are moving forward at unprecedented speed. The need for speed in COVID-19 vaccine creates challenges and enhancement danger.
  • Balancing the world’s need for a vaccine against the challenges of developing one and the dangers that an unsafe vaccine can pose is a key concern for researchers and regulators.
  • Immune enhancement phenomenon could be an issue to consider but, to date, there is no evidence of this happening with any of the vaccine projects underway.

CAJICA, Colombia. The world is pinning its hopes of a return to normalcy on a vaccine for COVID-19, one that is being developed at record speeds.

In the global race for a SARS-CoV-2 vaccine, there are now at least 149 contenders. The most advanced vaccine development programs are in phase III trials. Companies have accomplished in months what normally takes years or even decades. But the need for speed in COVID-19 vaccine creates challenges and enhancement danger.

Regulators have adjusted testing protocols to ensure the safety of vaccines, but haste can lead to waste and warnings have already surfaced of the dangers of rushing too much to get a COVID-19 vaccine out among the general public. 

One concern is the potential of immune enhancement phenomenon, an issue that was widely documented during trials for vaccines against the SARS-CoV-1 virus that caused Severe Acute Respiratory Syndrome (SARS) in 2003. 

For the time being, there is no evidence that the vaccines under development for COVID-19 would make the coronavirus worse. Also, many of the vaccines are being developed using techniques that were not available or in their infancy in 2003 and do not rely on deactivated versions of the virus. Still, scientists are keeping an eye on the potential danger of this enhancement phenomenon. 

Vaccines can take years

The SARS outbreak started in Southeast Asia and the disease spread to a few dozen countries. That virus was much more difficult to catch than SARS-CoV-2 but there are a lot of similarities between the two. Unlike SARS, the need for speed in COVID-19 vaccine creates challenges and enhancement danger.

After the 2003 outbreak, there was also a rush to find a vaccine against the virus. Research into a vaccine often had negative outcomes in preclinical trials, which are often done with animals before moving on to testing with people. Results of these early trials often showed this enhancement phenomenon and animals showed enhanced infection after immunization, particularly with vaccines developed from the actual virus. 

“It is difficult to evaluate whether these vaccines will prevent the disease in humans,” warned Chinese scientists in a study published in 2008 in the Journal of Immunology. “It is possible that a vaccine could be harmful, because immune-mediated enhancement of pathology has been reported in other animal coronavirus infections as well as in animals vaccinated with a modified vaccinia virus expressing SARS-CoV spike protein,” the research said.

The Lot 100 fail

The Chinese research references a vaccine disaster that took place in the 1960s in the U.S. when multinational pharmaceutical company Pfizer, from New York, was testing a novel vaccine against the respiratory syncytial virus (RSV). Patients were minors between two months and seven years of age. 

“Lot 100 not only failed to protect against wild-type (wt) RSV disease but also induced an exaggerated clinical response to wt RSV infection in infants who were RSV naive before vaccination,”another study conducted by Robert Dudas and Ruth Karron and published in 1998 in Clinical Microbiology Reviews said.

“Many vaccinees were hospitalized with LRI; in one study, the hospitalization rate of vaccinees approached 80% compared to 5% in controls,” it said.

Two infants that were part of the study, aged 14-months and 16-months, died after vaccination.

The trials were quickly stopped after those issues surfaced.

“It seems clear that infants who received this vaccine were not protected against natural infection and also, when they became naturally infected their illness was more severe than that seen in cohorts who received a similar parainfluenza type 1 vaccine,” another study published in the American Journal of Epidemiology in 1969, just a few years after the disaster, said.

To date, there is no commercial vaccine against RSV despite the efforts of research groups around the world to develop a vaccine that would prevent some 100,000 deaths every year.

Still, there are efforts underway to get one to the market. In June 2020, Pfizer itself announced a study to test an RSV vaccine candidate in pregnant women to test the efficacy on infants born from immunised pregnant women. Two months earlier, the company announced positive results from a Phase 2b proof-of-concept study.

According to the World Health Organization, there are at least 27 diseases for which vaccines are available but some of these vaccines have proven harder to develop than others. A malaria vaccine, for example, prove to be very elusive and was only developed over the past couple of years. It was similar with a dengue vaccine although it does not provide complete protection. As of 2012, the WHO estimated that 2.5 million deaths were prevented every year through the use of vaccines.

The Hepatitis concern

The need for speed in COVID-19 vaccine creates challenges and enhancement danger. The enhancement phenomenon is not the only concern. Another is the possibility of a stronger coronavirus circling in the respiratory system of vaccinated people as well as affecting other organs like the liver. 

While assessing the behavior of a SARS-CoV-1 vaccine in animal models using ferrets, scientists confirmed that one of the vaccines on trials enhanced pathologies affecting the liver tissue.

“Our data suggest that vaccination with rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis,” researchers said in a study published in 2004 in the Journal of Virology.

Enhancing SARS-CoV

“As the inflammatory response is strongly implicated in the pathogenesis of SARS, a full understanding of the mechanism of protective immunity against SARS-CoV in humans is critical in the development of a safe prophylactic vaccine for use in humans,”two scientists wrote in a paper published in 2009. One of them was from the University of Oxford.

Over the past couple of decades, multiple researchers have published findings on the enhancement phenomenon.

“One protein, the product of SARS-CoV ORF6, converted a sublethal infection to a uniformly lethal encephalitis and enhanced virus growth in tissue culture cells,” reported one of the studies.

Whether something like this can happen with a SARS-CoV-2 vaccine is unclear. However, the similarities between the two viruses, the one from 2003 and the one that is now making its way around the world now, are a concern for the scientific community.

“SARS-CoV-2 and SARS-CoV share 79.6% sequence identity, use the same entry receptor (ACE2) and cause similar acute respiratory syndromes. As such, key insights from studies of the immune response to SARS-CoV should be considered when developing vaccines for SARS-CoV-2,” Akiko Iwasaki and Yexin Yang wrote in a paper published last April in Nature Reviews Immunology.

“There is a desperate need for effective therapies and vaccines for SARS-CoV-2 to mitigate the growing economic crisis that has ensued from societal lockdown. Vaccines are being developed at an unprecedented speed and are already in clinical trials, without preclinical testing for safety and efficacy. Yet, safety evaluation of candidate vaccines must not be overlooked,” they said.