A safe, effective vaccine by December 2020 or January 2021?
Following the race to develop a COVID-19 vaccine is both heartening and dizzying. It’s heartening because it seems to be a race that will have a winner - perhaps several of them. It’s dizzying because the vaccines and their developers are jockeying for position, and projected timeline seems to change almost daily depending on the early results and who’s doing the talking.
Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Disease (NIAID), has been a cautious but optimistic voice about vaccine development for months now, although his institute does have a dog in this fight: NIAID is collaborating with Moderna on one of the most promising vaccines. Testifying before a Senate committee on May 12, Fauci stuck to the 12-18 month timetable he has mentioned often but added an “if” to the “when.” “You can have everything you think that’s in place and you don’t induce the kind of immune response that turns out to be protective and durably protective.” In an interview with NPR 10 days later, Fauci said, “We could have a vaccine that we could begin to deploy at the end of this calendar year - December 2020 or into January 2021.” And in a Q&A transcript that Stat posted on June 1, Fauci spoke of having a “significant number of doses” available by the end of this year or by early 2021. “So I think it’s aspirational, but it’s certainly doable,” said Fauci, in the transcript.
Meanwhile, President Donald Trump announced Operation Warp Speed in May to accelerate vaccine development for COVID-19 at an unheard of - some say unrealistic - pace. The selection of Moncef Slaoui, Ph.D., former head of GlaxoSmithKline’s vaccine division, as its chief adviser garnered praise. Later in May, the effort lived up to its name when it announced that it was plowing $1.2 billion into hastening development of a vaccine that University of Oxford researchers and AstraZeneca are working on. A press release about the funds from the Department of Health and Human Services (HHS) noted that HHS and AstraZeneca are collaborating to make 300 million doses, “with the first doses delivered as early as October 2020.”
Others are also talking optimistically about a sooner-rather-later schedule for a COVID-19 vaccine that would might be ready before winter, when many experts expect a second wave of cases because coronaviruses are seasonal. Part of the U.S. vaccine strategy as described by Fauci and others is to start manufacturing doses of vaccine candidates before the evidence of efficacy is in. “Fortunately, the U.S. is in the situation to scale up manufacture of vaccines even before you know they are going to work - maybe as early as the fall with billions of doses. That is the hope,” said National Institutes of Health Director Francis Collins, M.D., Ph.D., in a JAMA Network video event in May. “I don’t want to be over the top in confidence about that, but I can ensure you that everyone in the public-private partnership is doing everything they can to make that happen.”
Meanwhile, China also has an aggressive vaccine development program. Bloomberg reported recently that five vaccines developed by Chinese companies are in human trials and that one candidate, a joint project of the China National Biotec Group and the Beijing Institute of Biological Products, has completed phase 2 testing.
The go-go approach to COVID-19 vaccine development is causing some concern about consequences if anything goes seriously wrong with an approved vaccine. Anti-vaccine groups and social media influencers will certainly pounce if there are problems with safety and efficacy - especially safety. Conspiracy theories about the COVID-19 vaccines are already circulating on the internet. In May, a 26-minute video called “Plandemic” got millions of views before taken down by Facebook and YouTube. According to several articles about the video, it spins conspiracy theories about COVID-19 and big pharma, Bill Gates and the World Health Organization (WHO).
Challenge trials ethics
So far, though, the speed of vaccine development has been mainly impressive. The public-private partnerships among pharmaceutical manufacturers, academic researchers and government agencies resulted in phase 1 trials starting in record time. “From the very first moment the viral RNA sequence was made public … the first trial (Moderna) got started 63 days later,” Collins said in the JAMA Network video. “The phase 1 results look very promising - strong enough to say we are ready to go on to phase 2.”
Collins explained how the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative is developing a harmonized master protocol for adaptive trials of multiple vaccines, as well as a trial network that could enroll as many as 100,000 volunteers in areas where COVID-19 is actively circulating. Although there are some surrogate markers for efficacy, such as levels of neutralizing antibodies, the clearest “efficacy signal” will be whether a vaccine has a protective effect - in areas where COVID-19 is actively circulating - against infection with SARS-CoV-2, the virus that causes COVID-19.
“You have to test it in a place (where) the vaccine is actively circulating. You won’t know if it works if the vaccine is not actively around them,” Collins said.
Another possible way of assessing efficacy is through “challenge trials,” which would involve purposely exposing healthy volunteers to SARS-CoV-2; some volunteers would receive the experimental vaccine and some, a placebo. A difference in COVID-19 cases and severity between the two groups would indicate whether the vaccine was effective. However, challenge trials, which have been used to test other vaccines, raise troubling ethical issues in this case because they would involve exposing people to a possibly fatal illness. In an article in The Journal of Infectious Diseases, Nir Eyal at Rutgers, Marc Lipsitch at the Harvard T.H. Chan School of Public Health, and Peter G. Smith at the Tropical Epidemiology Group at the London School of Hygiene & Tropical Medicine outlined how the health risk might be mitigated - healthy volunteers, careful monitoring and so on.
They also parried the ethical objections with examples of other situations where people volunteer to take on possibly deadly risks for others: “We ask volunteer firefighters to rush into burning buildings, relatives to donate a live organ to loved ones, healthy volunteers to participate in drug and vaccine toxicity trials with no prospect of improving their health.”
By many counts, more than 100 COVID-19 vaccines are in some stage of development. At the beginning of the June, the WHO published a list that included 10 candidates in “clinical evaluation” - meaning in human clinical trials - and 123 in preclinical evaluation. Stat is keeping a COVID-19 vaccine tracker (and a separate one for treatment). As we went to press, it listed six vaccines as being in phase 1 trials and Moderna’s as the only one in phase 2. The company said volunteers for the phase 2 trial, which is designed to eventually include 600 study subjects, started getting the vaccine on May 29.
Moderna reported partial results from the phase 1 trial in a press release, but Fauci and others were critical of the lack of full report. The Regulatory Affairs Professionals Society is also keeping a user-friendly vaccine tracker that listed eight vaccines as being in clinical trials as we went to press. Topping its list (and absent from Stat’s and WHO’s) is a phase 2/3 trial of the 100-year-old bacillus Calmette-GuÃ©rin, a vaccine used to protect against tuberculosis.
Christine Blank is a freelance writer based in Orlando, Florida.