The science behind the leading COVID-19 vaccine candidates and when can we expect commercially available vaccine(s)
Although politically comforting and expedient, science does not support the principle of "herd immunity" for controlling the COVID-19 pandemic. Herd immunity is the term used when a sufficient number of individuals within a population become infected and immune, so the virus will no longer be able to circulate. Herd immunity has never been achieved with any disease without an effective vaccine stimulating durable immunity. Currently, there is insufficient knowledge concerning the antibody status of those recovering from COVID-19 irrespective of whether they were asymptomatic or required supportive treatment. Besides the increasing mortality due to the virus, the proponents of herd-immunity ignore the long-term consequences of infection. The virus can cause both cardiac and neural changes in addition to fatigue in the so-called “long haulers.” Therefore, the pandemic cannot be controlled until there is a safe and effective vaccine developed and administered to a significant number of people worldwide. This article will discuss the science behind the leading COVID-19 vaccine candidates and when can we expect commercially available vaccine(s).
There are more than 120 coronavirus vaccine candidates in various stages of development around the world, including some 50 currently in human studies. The four most prominent ones in the United States, with large-scale phase three clinical trials nearly finished, come from Moderna, Pfizer, Johnson & Johnson and the U.K.'s AstraZeneca will be covered in this article.
These companies are attempting to pull off the near impossible: Take a vaccine development process, which normally requires up to a decade, and compress it into a year-and-a-half timeline. In addition, initially developed vaccines don't have the greatest of track records (just 34% succeed, according to one study by MIT). Normally vaccines require four-phase testing to be approved by the FDA, which takes two years to complete, and the vaccine must provide at least 75% protection. However, due to the current state of ever-increasing infections worldwide, the FDA has promised to approve a vaccine after phase three trials if they are at least 50% effective. A 50%-effective vaccine will not totally prevent infection, viral spread or clinical disease in all individuals; however, it will provide a significant reduction in clinical disease, which will reduce hospitalizations and death rates.
These vaccine candidates have wildly divergent action mechanisms. They affect your cells and immune system in very different ways. Here's how some of that science works.
This vaccine uses viral messenger RNA (or mRNA) technology. Moderna’s COVID candidate, mRNA-1273, introduces a mRNA sequence (the viral genetic molecule, which tells cells what to build) into a human cell. The mRNA produces a specific part of the viral spike protein. This viral protein is recognized by the immune system to produce specific neutralizing antibodies, which can attach to the viral spike protein to prevent the virus from attaching and entering into the human cell. A caveat for this vaccine is that it requires ultra-cold refrigeration in order to preserve its various components. An ultra-cold freezer requires negative 112 degrees Fahrenheit. This requires that the vaccine must be kept in a specialized liquid nitrogen container. Also, Moderna's vaccine requires a second dose three weeks after the first.
Pfizer's vaccine also uses the mRNA technology. However, the company has a significantly bigger footprint in the pharmaceutical world as a $51 billion-plus revenue firm (and the logistics and manufacturing advantages which come with that, including a specialized case to ship its own vaccines.)
But, just as with Moderna, Pfizer will face the issue of storage and delivery given the mRNA technology its experimental therapy relies on. However, they created a device which can track the temperature and exact location of any dose being shipped across the country or the world.
These mRNA vaccines must be used within a two-week period, so it will need to be distributed by plane or a vehicle needing refrigeration. Much like the Moderna tech, Pfizer and its partners' vaccine would seek to turn your cells into antibody-producing machines, at least temporarily, to shut the virus down. Pfizer’s initial studies indicate that it can induce a similar level of immunity in all age individuals.
AstraZeneca, the British pharmaceutical giant working in tandem with the University of Oxford, is working on a vaccine in what's called a “non-replicating ChAdOx1 recombinant vaccine.” The virus mRNA which produces the viral spike protein is inserted into a none replicating adenovirus. This common cold live virus serves as a carrier for the mRNA and can infect human’s cells introducing the coronavirus mRNA. The mRNA then stimulates the immune response targeting the viral spike protein. However, the adenovirus cannot replicate in human cells, therefore it will not produce a cold. In addition, this is the first vaccine that has been shown to also produce T-cells. The T-cell response represents the second arm of the immune system and works by killing the virus before it can attach to a human cell.
Johnson & Johnson
Johnson & Johnson has expressed optimism about its coronavirus vaccine candidate, especially because it claims it can be effective with just a single dose and results in no detectable virus in the lower respiratory tract after exposure to SARS-CoV-2.
Like the AstraZeneca candidate, Johnson & Johnson uses the recombinant adenovirus vaccine as a carrier to insert the viral mRNA in the human cell. On the logistics side, this vaccine does not need the ultra-cooling like Moderna and Pfizer, possibly being able to be stored in more conventional refrigerators for a longer time.
During the phase three trials of all four vaccine candidates, high levels of neutralizing antibodies have been produced with mild adverse reactions, which may include pain at the injection site, fever, body aches, headaches and tiredness, that last no more than 48 hours.
There are many other vaccines in various stages of development, with potentially hundreds internationally in preclinical and clinical stages. These companies are relying on everything from inactivated subunit viral vaccines, synthetically made antibodies, to spike protein-blocking compounds, messenger RNA and adenoviral recombinant vaccines.
Despite the efforts of these pharmaceutical manufacturers, a vaccine will not likely be available until the beginning of 2021. Pfizer, the apparent leader in the race, has yet to conclude the evaluation of their phase three trial involving 40,000 participants conducted in the U.S., Brazil, Argentina, South Africa, Germany and Turkey. Recent preliminary results of its trial showed that it provided 90% protection during a short time frame. However, these results require statistical analysis and peer review before approval by the FDA. However, it is possible that the FDA could provide them with an emergency approval that could start administration prior to the end of the year. Results of Moderna’s mRNA vaccine are expected soon and the other two aforementioned companies’ products will take a while longer to reach FDA analysis. It must be remembered that it is not the first vaccine to be available that is important, rather it is the most effective one over an extended period of time. It is possible that several vaccines will be approved and available at the same time, and consumers will have a choice to make their own decisions as to which one to receive.
However, the earliest vaccines, which are approved, will provide only sufficient quantities to commence distribution to priority groups, including first responders, the elderly and those with predisposing conditions. Appropriate monitoring of recipients will be required for at least three months after initiating mass vaccination to distinguish between any possible adverse vaccine reactions and the large number of spontaneous but unrelated clinical conditions and mortalities that are sure to occur among recipients of the vaccine.
Mass vaccination of the general public will impose logistic challenges in distributing and administering a biological product that requires a critical cold chain. The earliest that we can expect this to occur will be in midspring. The reluctance of a high proportion of the U.S. population to receive a vaccine will obviously reduce the proportion of those that become immune within the population. It is yet unknown whether these vaccines can develop sufficient levels of antibodies and/or T-cells, which will provide protection from clinical effects or reduce the extent of virus shedding. An additional unknown is the durability of this immune response in the face of ongoing viral infections and the possible mutation of SARS-CoV-2 over time. It is possible that, as with other coronavirus infections, annual revaccination using newly adjusted viral subtypes, which may emerge, may be required, but this challenge is in the future. Those of the population who are a low risk of becoming infected and/or developing clinical disease might want to wait to receive a vaccine until they have seen the results of a larger vaccinated population.
It is accepted that there will be a delay in obtaining sufficient quantities of presumably effective vaccines, logistic complications associated with distribution and administration and reluctance to be immunized. Therefore, we must continue to adopt rapid testing for COVID-19 with strict quarantine of those shown to be exposed, contact tracing, masking, sanitation and hygiene, social distancing and avoiding crowds.
The true efficacy of these first-generation vaccines will not be fully known until millions of people have received them over an extended period of time (months or even years). These first vaccines will undoubtedly be altered or replaced with second-generation vaccines, which will produce at least 60% to 70% protection for one year and require only one administration and standard refrigeration storage, as is typically seen with influenza vaccines. The time frame for these improved vaccines may be several years.
About Joseph Giambrone:
Joseph Giambrone is a professor emeritus in Auburn University’s Department of Poultry Science with a joint appointment in the Department of Pathobiology in the College of Veterinary Medicine. During his graduate research career at the University of Delaware, he was part of a research group that developed the first vaccine against an antigenic variant of an avian coronavirus. During a sabbatical leave during his tenure at Auburn, he was part of a research group in Australia that sequenced the entire genome of antigenic variant of a coronavirus of chickens. During his 42-year research career as a molecular virologist, immunologist and epidemiologist, he has made critical advancements in understanding the ecology of viral pathogens, led efforts to improve detection and surveillance of viral diseases and developed new and effective vaccines and vaccine strategies to protect commercially reared chickens as well as pathogens, such as avian influenza viruses, which have spilled over into human populations. His research has had a profound impact on practices used today to reduce the incidence and severity of viral diseases of commercially reared poultry as well in human populations.
Joseph Giambrone is a professor emeritus in Auburn University’s Department of Poultry Science with a joint appointment in the Department of Pathobiology in the College of Veterinary Medicine.
Auburn University is a nationally ranked land grant institution recognized for its commitment to world-class scholarship, interdisciplinary research with an elite, top-tier Carnegie R1 classification, life-changing outreach with Carnegie’s Community Engagement designation and an undergraduate education experience second to none. Auburn is home to more than 30,000 students, and its faculty and research partners collaborate to develop and deliver meaningful scholarship, science and technology-based advancements that meet pressing regional, national and global needs. Auburn’s commitment to active student engagement, professional success and public/private partnership drives a growing reputation for outreach and extension that delivers broad economic, health and societal impact.