Since the start of the novel coronavirus pandemic, a number of pharmaceutical companies and government agencies have rushed to create a vaccine on a timeline greatly accelerated compared to what is normal for the industry. Suffice to say, none of the many vaccine attempts have been widely distributed yet, and there is no clear front-runner; even the ones that have been rushed to production, like the Russian vaccine, come with caveats.
This article first appeared in Salon.
President Donald Trump — who once stated his belief that vaccines could be linked to autism — is determined to rush a vaccine to production, so much so that 62 percent of Americans are concerned he will push one out to the public before it is confirmed to be safe and effective. A group of pharmaceutical companies released a joint statement earlier this week vowing to not rush the vaccine development process at the expense of safety, citing the need “to uphold the integrity of the scientific process.”
Vaccines take time to develop, whether politicians find that convenient or otherwise. The reason has to do with immunology and logistics: vaccines need to tested in small groups to make sure they’re safe and that they work; then in bigger groups, where some patients get a placebo; then, those groups have to be observed over time, as Dr. Eugene Shapiro, professor of pediatrics and epidemiology at Yale University, explained to Salon.
If done wrong, or if steps are skipped, all kinds of problems can emerge. An untested, rush-job vaccine could cause “inflammatory reactions in the body when the body rushes to try to generate antibodies and T-cells against the ‘antigens’ or proteins in the vaccine formulation,” as Dr. Monica Gandhi, infectious disease doctor and professor of medicine at the University of California–San Francisco, told Salon. This explains the case of spinal inflammation in one patient who received AstraZeneca’s coronavirus vaccine (more on that in a moment).
“Vaccine development is a high risk undertaking, especially for a new disease,” Dr. Albert Ko, department chair and professor of epidemiology and of medicine at Yale University, told Salon by email. “The development and evaluation of multiple types of vaccine candidates mitigates the risk of failure and increases the hope that we will have successful safe and effective vaccines.”
What, exactly, are those multiple vaccine candidates? To list just the most prominent ones, in the United States and Europe you have AstraZeneca (which is working in partnership with Oxford University), Moderna (which has partnered with the National Institutes of Health), Pfizer (which is working with its German partner BioNTech and the Chinese drug maker Fosun Pharma), Merck, Inovio, Johnson & Johnson, Novavax and Sanofi (which is working with GlaxoSmithKline). You also have Russia’s vaccine and the Chinese company CanSino, both of which have made claims of progress.
Here is where each one stands currently.
Oxford University/AstraZeneca Vaccine
The latest news from AstraZeneca has not been promising, as the company recently had to address a safety signal (a negative event possibly caused by a medicine that requires further investigation) during Phase Three trials of its vaccine testing. Phase Three trials are, according to the U.S. Department of Health and Human Services, “conducted to confirm and expand on safety and effectiveness results from Phase One and Two trials, to compare the drug to standard therapies for the disease or condition being studied, and to evaluate the overall risks and benefits of the drug.”
During its Phase Three trial, a patient in the United Kingdom experienced a suspected adverse reaction serious enough to prompt AstraZeneca to put a hold on its study. The company explained that a female volunteer experienced spinal inflammation and other symptoms consistent with a neurological disorder called transverse myelitis. Another patient also experienced neurological symptoms after receiving the vaccine candidate in July, although because the participant was later diagnosed with multiple sclerosis, scientists ruled that the reaction was unrelated to their potential vaccine. The company temporarily halted its clinical trial after that event as well.
Salon reached out to Oxford University by email, where a spokesperson referred this journalist to a website that provides updates on its COVID-19 vaccine testing as well as a link where the public can find more general information.
“This particular candidate from the AstraZeneca company had a serious adverse event, which means you put the rest of the enrollment of individual volunteers on hold until you can work out precisely what went on,” Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases (NIAID), told CBS News on Wednesday. “It’s really one of the safety valves that you have on clinical trials such as this, so it’s unfortunate that it happened. Hopefully, they’ll work it out and be able to proceed along with the remainder of the trial but you don’t know. They need to investigate it further.”
AstraZeneca CEO Pascal Soriot expressed confidence on Thursday, saying that, if the safety committee says they can restart trials, they could still know whether their vaccine protects people from COVID-19 before the end of 2020.
Ko pointed to the AstraZeneca trial as an example of the risks innate to vaccine research.
“It is too early to know if these vaccine candidates will in fact be safe and effective,” Ko wrote to Salon. “We will only understand whether this will be the case, once Phase III clinical trials are completed and produce evidence. The temporary halting of the AstraZeneca trial for an adverse event, for which we don’t know if its related to the vaccine, underlies the importance of performing these rigorous trials in large numbers of people.”
Moderna and other U.S. and European pharmaceutical companies
Moderna has gained particular attention because the Department of Health and Human Services last month announced that the Trump administration is investing $1.5 billion to produce 100 million doses of a vaccine, with an option to purchase an additional 400 million doses. Trump himself has played up Moderna’s supposed speed in developing a vaccine, bragging in July that Moderna entered Phase Three clinical trials in “record time.”
Indeed, Moderna, announced last week that it was slowing trial enrollment because it wants more individuals from minority groups to participate in the study. “We want to ensure we have data for all the people who could benefit and be protected,” CEO Stephane Bancel explained in an interview with CNBC. The pharmaceutical company started its Phrase Three trial on July 27, the same day that pharmaceutical giant Pfizer announced it was entering Phase Two and Three trials. Pfizer is also participating in Operation Warp Speed (a federal public-private partnership program to find a vaccine for the coronavirus), and in July received an initial order from the US government of 100 million doses for $1.95 billion, with the option to later purchase an additional 500 million additional doses.
“We continuously monitor and evaluate the safety profile of the Pfizer vaccine candidate, including review by an external, independent Data Monitoring Committee (DMC) composed of vaccine safety experts,” a spokesperson for Pfizer told Salon by email. “To date, no safety signal has been identified, and the DMC has recently recommended continuing the trial as planned.” The spokesperson also said that the company has enrolled more than 25,000 participants and shared a link where it provides updates to the public.
Things have been less dramatic with other American and European companies that are working on a vaccine. According to MarketWatch, Inovio announced this week that it will launch Phases Two and Three of its vaccine trials if given approval by the FDA. The drug companies GlaxoSmithKline and Sanofi announced last week that they are starting clinical trials. Merck announced last week that it is starting human trials on one of its vaccine candidates “fairly soon.” Novavax is expected to begin Phase Three trials in October. A representative from Johnson & Johnson told Salon by email that “we anticipate that our Phase Three trial will initiate later in September pending discussions with regulators, and possible first vaccine batches for potential emergency use available in early 2021, pending results from ongoing and upcoming clinical studies.”
The Russian government’s vaccine
By contrast, the vaccine being developed by the Russian government has come under harsh scrutiny. The Russian government’s claim last month of having developed a successful vaccine was immediately met with skepticism from experts, who pointed out that it was tested on a very small number of volunteers (76) and that researchers had published only a sliver of its underlying data. More recently a letter from 26 scientists, most of them working at Italian universities, drew attention to how the Russian data on its Phase One/Two trials claimed a number of participants had the same antibody levels. The probability of this happening is very low, the scientists argued, although they added that it is difficult to truly scrutinize this data because they only have access to summaries published in the medical journal The Lancet rather than the original data itself.
The Gamaleya Institute, which is behind Russia’s vaccine and falls under the purview of Russia’s Ministry of Health, claimed that their organization had submitted all of the raw data to the medical journal The Lancet and insists that they are “authentic and accurate and were examined by five reviewers at The Lancet.” Naor Bar-Zeev, deputy director at John Hopkins Bloomberg School of Public Health, defended his peer review of the Russian data, arguing that “the results are plausible, and not very different to those seen with other AdV vectored products.”
CanSino’s vaccine (China)
When it comes to the Chinese company CanSino Biologics, outside scientists have claimed that its vaccine may not be effective. The vaccine candidate, Ad5-nCoV, was developed based on a common cold virus that many people have already been exposed to, and critics are concerned that existing antibodies against that virus might undermine the vaccine’s effectiveness. During an investor conference, chief scientific officer Zhu Tao responded to these criticisms by saying that “vaccine development is a practice-based science, and we should not blindly follow experts.” He claimed that experts have been wrong in the past. The CanSino vaccine is still in final stage trials, although it has been approved for use for members of the Chinese military.
The future of coronavirus vaccine research
Dr. Alfred Sommer, dean emeritus and professor of epidemiology at Johns Hopkins Bloomberg School of Public Health, explained to Salon how one can balance cautious optimism about a future vaccine with a healthy dose of realism.
“It is encouraging to see so many players in the field, many using very different platforms (forms of vaccines),” Sommer wrote to Salon. “This clearly increases the likelihood that at least one if not more of these vaccine candidates will prove safe and effective. Some are likely to prove more effective than others at reducing the risk of subsequent infection, and provide such protection for longer periods of time. The lessons we learn from each approach might well increase the likelihood, and the speed, at which even more effective vaccines are developed.”
Sommer added that “there is no guarantee any of the present candidates will prove sufficiently effective and free of side-effects for use in mass immunization campaigns; particularly among the elderly, whose immune systems are generally weaker and therefore less likely to produce a protective response, and whose risk of serious disease from infection is much higher than among younger individuals.” He expressed hope on a personal level that “one or more of these vaccines” will be “available early in 2021” and “will provide adequate levels of protection to justify mass immunization, even if better vaccines are subsequently produced and an additional vaccination is needed to gain highly protective, lasting immunity.”
Dr. Georges Benjamin, executive director of the American Public Health Association (APHA) and former secretary of health in Maryland, expressed a similar point.
“The current progress on a COVID is on track as a phase three trial,” Benjamin wrote. “So far the complications that have been reported publicly are minor with the one exception of the one from the Oxford group that was reported yesterday. We don’t know yet what this complication of real means. I think we are on track to have meaningful answers by the end of the year about safety and efficacy. That does not mean we will have all of the answers by then for sure, but we will at least have a reasonable handle on which vaccines have a high degree of promise.”
He added, “If the studies show that any are safe and effective by the end of the year then we could see vaccination of priority populations by January 2021. Broad-based vaccinations would be available by early summer 2021.”