How Soon Can We Get a COVID-19 Vaccine?
The question to ask is whether the vaccine will be effective and safe
The COVID-19 pandemic is raging worldwide with the death toll now exceeding 920,000. In the United States alone 194,000 people have died of the disease. In the absence of an approved therapeutic drug to treat the disease, there is a mad rush among pharmaceutical companies and countries to bring a vaccine to the market. President Trump wants the FDA to grant emergency use authorization for an experimental coronavirus vaccine. The CDC has issued new guidance to all fifty states to distribute a vaccine to health care workers and other high-risk groups as soon as late October or early November. This directive was sent out on the same day that President Trump gave a speech to the Republican National Convention indicating that a vaccine might be available by Election Day. Dr. Moncef Slaoui, the chief scientific adviser to the Trump administration initiative tasked with the development of COVID-19 vaccines, when asked during an interview with National Public Radio, whether it is realistic to expect the vaccine to be available by late October, responded, “Yes, it’s [a] possibility but very unlikely.” The next day, Trump contradicted his chief adviser and again claimed that a vaccine will be available by the end of October. An “October surprise” may be a political ploy by an incumbent President with sagging poll numbers to try and boost his chance of reelection.
Worldwide, there are over 150 vaccines under development to provide protection against the novel coronavirus (SARS-CoV-2). The Chemical and Engineering News, a publication of the American Chemical Society had an article in its July 27, 2020 issue on the COVID-19 vaccine candidates and the clinical trials being conducted worldwide. This paper is based on that article, other scientific publications, news magazines, and news stories.
Historically, vaccine development used to be a long, arduous process that took years to produce results. It took thirty-four years to develop a vaccine for chickenpox. Yet, it took only four years to develop a vaccine for mumps. In the United States, the Food and Drug Administration (FDA) sets the rules for vaccine development and approval. The three phases of clinical trials in the process are illustrated in the graphics from the FDA.
The Operation Warp Speed initiative by the U.S. government has pledged $10 billion to develop and deliver 300 million doses of a safe, effective coronavirus vaccine as quickly as possible. At least seven vaccines (Pfizer, Moderna, AstraZeneca/Oxford, Sinovac/Chinese, Sputnik V/Russian, CanSino/Chinese, Sinopharam/Chinese) have made it to phase 3 clinical trials.
The Washington Post maintains an excellent site on the top coronavirus vaccines to watch. Vaccines work by teaching the body’s immune system to recognize and block the coronavirus. The goal is to trick our bodies to make the SARS-CoV-2 spike protein. The details on the four technologies employed by these groups have been summarized from the Washington Post site.
New technologies being used to deliver genetic materials to cells
- RNA vaccines contain a strip of genetic material within a fat bubble of the coronavirus. Once inside the cell, the RNA generates a protein found on the surface of the virus. The immune system, presented with the protein, learns to recognize the virus. These vaccines can be quickly designed and manufactured. However, no such vaccine has so far been approved for use outside of medical research.
- Viral-vectored vaccines use a virus that has been engineered to be harmless to carry a gene from the coronavirus into human cells and the immune system learns to recognize this coronavirus gene. Viral-vectored vaccines can be designed quickly. Booster shots may have to be given if people develop immunity to the viral vector.
- Weakened or inactivated virus vaccines employ an old-fashioned approach used in the earlier development of vaccines for polio, measles, mumps, and rubella. The virus is weakened so that it does not cause disease, but still triggers the immune system’s defenses. These vaccines typically take longer to manufacture.
- Subunit vaccines The companies that employ this technology use insect cells and yeast to produce the protein fragments. For example, the hepatitis B vaccine relies on a viral protein created by genetically engineered yeast.
Moderna and Pfizer are encoding instructions for the spike protein in mRNA (messenger RNA), which is delivered into our cells via lipid nanoparticles. CanSino and AstraZeneca (Oxford) have created adenoviral vector vaccines. Two of the most closely watched COVID-19 vaccines in the United States are the ones from Moderna and AstraZeneca/Oxford University. A peer-reviewed study on the Moderna vaccine was published on July 14, 2020, in the New England Journal of Medicine. On July 20, 2020, the British Medical Journal, Lancet published a peer-reviewed article on the AstraZeneca/Oxford vaccine.
On September 4, 2020, Lancet published a paper detailing the safety and the immunogenicity of the recombinant adenovirus vector-based COVID-19 vaccine named Sputnik V developed in Russia. The results of this study combined phases 1 and 2. The vaccine induced a strong immune response in all 76 participants and it appears to be safe. Large-scale clinical trials (phase 3) of the vaccine, involving over 40,000 people, were scheduled to begin in Russia in August and the results are expected to be released by the end of October 2020.
Based on the COVID-19 vaccine trial reports, most participants developed antibodies to the SARS-CoV-2 spike protein 2–4 weeks after vaccination. The amount of the antibody levels that bind to the spike protein are then measured. Only a handful of antibodies that bind at just the right spot, so-called neutralizing antibodies, will prevent infection. Moderna, Pfizer, Oxford, and Sputnik V vaccines, all measured neutralizing antibody levels in plasma from people who have recovered from a natural COVID-19 infection. One shot of the mRNA vaccines from Moderna and Pfizer was not enough to induce levels of neutralizing antibodies equal to the average levels found in convalescent plasma. A second shot of these vaccines induced high levels of antibodies, but levels began to decline rapidly two weeks later. It is too soon to know if the antibody levels for any of these vaccines will continue to decline or will reach a plateau.
Researchers studying convalescent plasma have noted that the average levels of antibodies developed after a SARS-CoV-2 infection are not particularly high, and some studies suggest that the antibody levels decline over time. An ideal COVID-19 vaccine, according to scientists, should induce antibody levels that significantly exceed average levels in convalescent plasma. It is important to watch for T cell responses too since T cells can help boost the antibody response. All the vaccine trials reported the presence of a T cell response. Given the small number of participants (76) in the Russian vaccine trials, scientists have raised concerns about the data published.
It has only been eight months since pharmaceutical and biotech firms began their efforts to produce a vaccine for COVID-19. Based on preliminary results from phase 1 and phase 2 trials, the scientists are cautiously optimistic that once the phase 3 trials are completed, one or more vaccines will be effective. It will require clinical trials involving hundreds of thousands of participants to establish long-term efficacy and safety.
Safety and side effects could present another sticking point. None of these four studies was large enough to determine if the vaccines cause rare reactions. All four vaccines caused systemic side effects, and higher dosages were linked to more frequent and more severe side effects. Although most of these side effects were considered mild or moderate, there is still the possibility that severe side effects could become more pronounced as the vaccines are tested in larger trials.
Trust is another critical element to be considered in the development of the COVID-19 vaccine and in the subsequent efforts to vaccinate the masses. Those participating in clinical trials must be able to trust that they will not be exposed to unnecessary and unacceptable risks. We all need to be able to trust that the vaccines that emerge are effective and safe. The key to both these elements is the existence of a thorough regulatory process, overseen by the FDA in the U.S. and the MHRA (Medicines and Healthcare products Regulatory Agency) in the U.K. The process appears to be working well at the moment in both countries.
On September 8, 2020, the phase 3 clinical trials of the COVID-19 vaccine being developed by AstraZeneca and the University of Oxford was put on hold in the U.K. This was because of an adverse neurological disorder in one of the participants. After a review by an independent committee of experts, the drugmaker AstraZeneca on Saturday, September 12, 2020, announced that the vaccine studies have resumed in the U.K. The clinical trials in other countries are still on hold and it is possible that this setback will impact a decision for early approval of the vaccine.
A cautionary public health tale from 1976
In February 1976, hundreds of soldiers at Fort Dix, N.J., contracted a new strain of the swine flu. It was an election year, and President Gerald Ford, who had risen to the presidency upon Richard Nixon’s resignation, was seeking his first full term. He requested an emergency appropriation of funds from Congress for the production of a vaccine to inoculate everyone in the United States. Of the 45 million vaccinated against the swine flu, an estimated 450 people developed the paralyzing neurological disease known as Guillain-Barré Syndrome and of those, more than 30 died. The government soon ended the mass vaccination effort. The public became skeptical of government-mandated vaccination efforts.
Unless a vaccine is deemed effective and safe, the majority of the population will be reluctant to get vaccinated. In a new poll from the Kaiser Family Foundation, 62 percent of respondents said they were concerned about a vaccine being authorized by the Food and Drug Administration (FDA) before it is proven effective and safe. In June 2020, FDA had to pull the emergency approval granted to the antimalarial drug, hydroxychloroquine touted by President Trump as a treatment for COVID-19. This time, it is not certain the FDA will risk its reputation and independence by granting emergency use authorization to a vaccine that has not completed the phase 3 trials and has undergone a peer-reviewed evaluation of data. The vaccine developers are big pharmaceutical companies who also have to protect their reputations. On Tuesday, September 8, 2020, nine vaccine makers — including Pfizer, AstraZeneca, and Moderna— issued a public pledge not to seek government approval without extensive safety and effectiveness data.
FDA Guidelines for COVID-19 vaccine approval
As per the guidelines issued by the FDA, a COVID-19 vaccine could be approved for use in the U.S. if it will prevent the disease or decrease its severity by at least 50 percent. What it means is that if 100 people are vaccinated, 50 people will not get the disease. A 50% threshold may not sound like an impressive rate of prevention. The influenza vaccine used during the 2019–2020 flu season was reported to be only 45% effective. Among the 55% who still got the flu, for the vast majority, their disease was milder. According to Dr. Bill Miller, an epidemiologist with The Ohio State University, “…the vaccine will reduce the severity of disease in the other 50% who do get sick. It may mean that people are less likely to be hospitalized, require ICU care, or die.”
Who will receive the vaccine when approved and in what order?
When a vaccine is approved, the number of doses available is not going to be sufficient to vaccinate the whole population all at once. Healthcare workers in the frontline and first responders should receive priority followed by older adults with underlying conditions. The National Academies of Sciences, Engineering, and Medicine has released a draft framework to help policymakers fairly allocate and distribute the vaccine. The Johns Hopkins Center for Health Security has published a report in which their experts have also come up with an interim framework for COVID-19 vaccine allocation and distribution.
It is expected that one or more of the COVID-19 vaccine candidates in phase 3 clinical trials may receive FDA approval for use this year. Still, it may take several months and probably until the end of 2021for everyone to be inoculated.
The major publications that were relied upon for information in this paper are linked below.
