The race for the holy grail: Is a swift COVID-19 vaccine within reach?
Article information and share options
UPDATED 30th JULY 2020.
Until we have mass immunity to COVID-19, the world cannot fully relax – nether psychologically nor practically.
But how do we reach immunity? It can happen in two ways, each with its own costs:
- We develop herd immunity by allowing the disease to run its course, which means accepting a large number of lives lost. There is currently a discussion over how long individual immunity lasts, and whether herd immunity can develop.
- We develop a vaccine and deploy it on a mass scale which also has various economic and social considerations. A vaccine has never been created for a coronavirus before, and the length of protection it could offer is still unknown, with booster vaccines (perhaps annually) being needed for full protection.
There are many encouraging signs in the development of a COVID-19 vaccine, with numerous parallel studies underway and accelerated support for trials and regulatory approval. Generous funding is flowing from government, non-government and commercial sources accompanied by an unprecedented level of international cooperation. Currently there are five strong vaccine candidates being tested in late stage clinical trials. While there is a lot of hope for a successful development, the road from testing to general use is a long one.
However, vaccine development typically takes many years and individual trials have a low probability of success. Viruses are mutable and immunity may be short lived, although coronaviruses are less susceptible to mutation than others. Vaccine production and distribution will take time, may become politicised and some may refuse vaccination. Different target groups, particularly the elderly, may require different doses and efficacy may also vary.
The generally accepted scientific view is the earliest we could expect a functional vaccine will be early to mid-2021, but the path to mass COVID-19 immunity will likely prove somewhat longer.
This article is an update of our earlier publication that keeps you abreast on the pursuit of a COVID-19 vaccine. We examine the most prominent vaccine candidates that are already in late stage clinical trials, on the fast track to being released. We'll review the platforms being used to develop a candidate vaccine, the expected timeline and the development of alternative immunotherapies.
As the five candidates enter the last, longest, testing phase, the race has truly begun.
After months of infection across the world, we have come to realise a stark truth: Mass immunity to COVID-19, without enduring significant loss of life, might only be achieved through a successful and long-lasting vaccine. Developing a safe vaccine for a new illness is neither easy nor straightforward. Under current best-case assumptions, leading experts think it could take 12 to 18 months with an accelerated approval process and research moving at unprecedented speed.
Rapid progress is being made through concerted and coordinated efforts around the world. This started with China’s rapid sequencing of SARS-CoV-2 genetic material and subsequent global sharing of research, aided by substantial funding from private companies, governments and non-governmental organisations. The Coalition for Epidemic Preparedness Innovations (CEPI) has already received government funding of more than USD 1 billion toward a target of USD 2 billion for rapid investment and development of COVID-19 vaccine candidates.1,2
On 4 May 2020, the World Health Organization (WHO) organised a telethon to raise USD 8 billion from 40 countries to research, manufacture and distribute a possible vaccine and treatments for COVID-19. On 15 May, the US government announced federal funding for a fast-track program called Operation Warp Speed. The goal is to place diverse vaccine candidates in clinical trials by the Autumn of 2020 and manufacture 300 million doses of a safe and effective vaccine by January 2021.
When will a vaccine be available?
The earliest we can expect a successful vaccine candidate could be 12 to 18 months, which would be a huge advance over traditional timelines. Vaccine development typically takes more than a decade with approval success rates of 10-15% as it moves from phase 1 to successful phase 3 clinical trials. Assuming the odds are overcome and regulatory authorities speed reviews, an initial vaccine may be produced by early to mid-2021, at the earliest.
There are good reasons to allow sufficient time to check for safety and efficacy. It's critical to ensure the vaccine does not induce a counterproductive or even dangerous immune system reaction (known as immune enhancement), and that the vaccine generates a long-term protective immune response, especially in the most vulnerable ageing population3. This is particularly important given the premise that 60% of populations need to be immunised to achieve sufficient levels of herd immunity.
Assuming a successful vaccine is found, a secondary challenge will be global manufacturing and distribution. Production capacity will likely not meet the initial huge demand, distribution will take time and politics may intervene. It is also likely that more than one round of vaccination will be needed to achieve (even temporary) immunity. First recipients of the vaccine would probably be emergency medical service providers, first responders and healthcare workers, followed by the elderly in the highest risk groups4.
A further uncertainty of any COVID-19 vaccine is the duration of immunity. For comparison, there are four seasonal circulating coronaviruses that cause the mild common cold (229E, NL63, OC43 & HKU1). Our natural immunity to these is typically only short-term, although it's highly unlikely to be re-infected in the same or following season. Experience with previous SARS and MERS coronavirus epidemics suggests that immunity could last up to three years or more and recovered patients have a low risk of reinfection5.
Early evidence suggests people who recovered from COVID-19 are likely to be immune from reinfection in the short term, however the level of virus-specific antibodies seems to depend on severity of disease6. A recent study showed that levels of antibodies were significantly lower in the asymptomatic group than in the symptomatic group during the acute phase of infection. This suggests asymptomatic patients may have had a weaker immune response to SARS-CoV-2 infection7. It remains unclear whether an immune response generated by a vaccination could decrease over time.
To determine this more precisely, longitudinal serological studies are required to monitor patient immunity after infection and vaccine immunisation over a longer time period. Such studies are underway at the Centre for Applied Microbiology and Research at Porton Down in the UK as well as in other research centres around the world. These studies are being strongly recommended by the WHO.
Ideally, a COVID-19 vaccine will provide protection for life, or at least many years. The WHO's current minimally acceptable and preferred profiles for COVID-19 vaccines set out a minimum protection of at least six months to a year with an efficacy of 50-70% on a population basis8.
From start to finish: developing a vaccine
Vaccine development normally requires two to five years before a clinical trial can begin. It's typical to have a three-step development process:
Step one: Pre-clinical studies
These typically involve laboratory and animal experiments, testing different strengths of the vaccine to find a dose that is safe, effective and non-toxic.
Step two: Clinical trials
Three phases of clinical testing are required prior to regulatory approval. Completing these stages can take years, even decades. However, COVID-19 clinical trials will be significantly accelerated.
Phase 1: To confirm a vaccine is safe for humans, 50-100 “healthy” volunteers are tested.
Phase 2: To assess preliminary efficacy, a few hundred volunteers participate in a “double blind” approach of randomised injections of either the vaccine candidate or a placebo. Neither testers nor those being tested are aware of which dose they are receiving.
Phase 3: The vaccine candidate is tested in a few hundred to a few thousand volunteers against the best existing available treatment (which is not applicable for COVID-19) to confirm its efficacy and safety. Except in very rare circumstances, the approval of a drug or vaccine would not be granted without success in phases 2 and 3.
Phase 4: Long-term post-approval surveillance on the safety, risks, benefits or best uses of the vaccine are compiled9.
Step three: Regulatory approval
Official approval by the US Food and Drug Administration (FDA) or other equivalent national bodies will confirm the vaccine’s effects have been reviewed, and the treatment is determined to provide benefits that outweigh its known and potential risks in the intended population.
Given the urgent demand for a COVID-19 vaccine, clinical trials are being fast-tracked and likely to be carried out in parallel across different countries and age groups10. More than one vaccine may ultimately be released – each targeting a different group at risk, as is often done for the seasonal flu vaccine.
Platforms for vaccine development
There are many different paths to developing a vaccine – some new and others well established. The most prominent platforms in phase 1-3 COVID-19 trials stimulate human immune response in one of two ways:
- Using viral DNA and RNA molecules coding for parts of the target pathogen, or
- Using viral vectors (replicating or non-replicating) or inactivated viruses which are essentially harmless viruses that express a SARS-CoV-2 specific antigen – that triggers the immune response.
In both cases, the delivered antigens are subsequently displayed to the body's immune cells. Whereas platforms based on DNA and RNA offer great speed and flexibility for manipulating antigens and rapid and scalable production, vaccines based on viral vectors provide long-term stability and induce strong immune responses.
Other platforms under development take a different approach and focus on viral elements that can be recognised by the immune system such as:
- short viral protein subunits
- rebuilt viral proteins
- weakened (attenuated) SARS-CoV-2 virus
The attenuated or inactivated virus may generate a stronger and more durable immune response with minimal to no risk of infection.
Based on data as of 27 July from the Vaccine Centre at the London School of Hygiene & Tropical Medicine
What will the vaccine target?
Antigens are proteins on the virus wall, which allow the virus to invade cells or reproduce. They also serve as a target for the host's immune system. Detailed knowledge of specific SARS-CoV-2 antigen(s) is limited. Most pipeline vaccines aim to induce an immune response against the viral Spike (S) protein. The S protein allows the virus to invade a host cell by binding to the cell surface receptor angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin system that controls blood pressure. However, it is still unclear how different forms and/or variants of the S protein used in different candidates relate to each other; and how strong immunity responses towards different antigens will be11.
There are concerns that excessive targeting of the S protein without enough focus on other structural elements of SARS-CoV-2 may cause the virus to mutate and lead to an immune exhaustion or immune escape. We already see a precedent for this in the influenza virus. Targeted antigens – haemaglutinin (H) and neuraminidase inhibitors(N) – mutate and lessen the effectiveness of the seasonal influenza vaccine.
Current COVID-19 vaccine candidate landscape
By end of July 2020, there were more than 200 vaccine candidates at varying stages of development. The Vaccine Centre at the London School of Hygiene & Tropical Medicine currently lists 31 COVID-19 vaccine candidates in clinical trial phases 1 to 3 and another 187 candidates in exploratory or preclinical stages8,11–13.
The most advanced and promising candidates include the seven listed in the below summary. Of these it's notable that Moderna started clinical testing of its mRNA-based vaccine just two months after sequence identification of COVID-19 (see table, end of document).
Six of the most prominent targeted vaccines
• mRNA-1273 from Moderna
An mRNA vaccine candidate encoding for a prefusion stabilised form of the S-protein, which binds to the host cell. The S-protein has been the target of vaccines against the coronaviruses responsible for Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The genetic sequence in SARS-CoV-2 is 80% similar to the S-protein in SARS. The vaccine relies on mRNA to kickstart the endogenous production of proteins similar enough to the virus that they trigger the body’s adaptive immune system to produce antibodies effective against the real virus.
On 25 May, Moderna began a Phase 2 clinical trial recruiting 600 adult participants to assess safety and differences in antibody response to two doses of its candidate vaccine, mRNA-1273. Expected completion is in 2021.
Encouraged by Phase 1 data, the company received an additional USD 472m from the US government on 26 July to support its late-stage clinical development including the expanded Phase 3 study of their vaccine candidate. The Phase 3 study began on 27 July and aims to enroll 30,000 US participants. The primary endpoint will be the prevention of symptomatic COVID-19. Key secondary endpoints include prevention of severe COVID-19 (as defined by the need for hospitalisation) and prevention of infection by the virus.
Moderna, closely in line with Operation Warp Speed and the NIH, said it remains on track to be able to deliver about 500 million doses per year, and possibly up to 1 billion doses per year, beginning in 2021. A key advantage of mRNA vaccines is the potential speed of production compared to other vaccine platforms. However, there has never been an approved mRNA vaccine or other mRNA based therapeutics for any condition14.
• AZD1222 from the University of Oxford
The AZD1222 coronavirus vaccine candidate, formerly known as ChAdOx1 nCoV-19 is based on an adenovirus vector encoding for the S-protein of SARS-CoV-2. A preliminary report of a Phase1/2 study published on 20 July, showed a single dose of AZD1222 resulted in a 4-fold increase in antibodies to the virus spike protein in 95% of participants one month after injection15.
The vaccine candidate has progressed into late-stage Phase 2/3 clinical trials in more than 30,000 people in the UK, Brazil, and South Africa and is due to start in the US. If the vaccine is proven to be safe and effective, the first doses to be produced are anticipated to be available in early 2021. Vaccines will be released on a rolling basis as production is completed, and the full quota of 300 million doses is expected to be available by July 2021.
• CoronaVac from Sinovac Biotech
This candidate is based on an inactivated SARS-CoV-2 virus by growing the whole virus in a lab and then killing it, similar to how polio shots are made.
On 13 June, Sinovac announced positive preliminary results of their Phase 1/2 clinical trial in China, which showed favorable immunogenicity and safety profiles after vaccinating a total of 743 volunteers. The company expects to complete the phase II trial at the end of 2020.
Sinovac has partnered with several companies outside China for Phase 3 efficacy studies, and on 2 July, Reuters reported that a Phase 3 study will recruit nearly 9,000 healthcare professionals working in COVID-19 specialised facilities in 12 clinical sites, across Brazil16. Sinovac also announced it's constructing a commercial vaccine production plant in China that is expected to manufacture up to 100 million doses of CoronaVac annually17. On 16 May, Health Canada approved human clinical trials for possible coronavirus vaccine to be conducted in Canada. On 25 June, China's Central Military Commission approved the use of the vaccine by the military for a period of one year. So far, there has been little publicly- available information on this candidate.
• BNT162 (a1, b1, b2, c2) from BioNTech, Fosun Pharma, Pfizer
Pfizer, in concert with BioNTech, a German company, is also developing an mRNA vaccine that encodes for the SARS-CoV-2 spike (S) protein. The BNT162 program is evaluating at least 4 experimental vaccines, each of which represents a unique combination of messenger RNA (mRNA) format and target antigen.
Currently, the developers are conducting Phase1/2trials that focus on dose-ranging studies among 4 candidates. Preliminary data from the US demonstrated that BNT162b1 could be administered in a dose that was well tolerated and generated dose-dependent immunogenicity. Subject to regulatory approval, the companies are expecting to start a Phase 2/3 trial as during the summer of 2020 and are anticipating enrolling up to 30,000 subjects.
If the ongoing studies are successful and the vaccine candidate receives regulatory approval, the companies expect to manufacture up to 100 million doses by the end of 2020 and potentially more than 1.2 billion doses by the end of 2021. On 22 July, Pfizer and BioNTech announced an agreement with the US government which will receive 100 million doses of BNT162 after Pfizer successfully manufactures and obtains approval or emergency use authorization from the US FDA. The US government also has an option to acquire an additional 500 million doses of the vaccine.
• Inactivated vaccine from the Wuhan Institute of Biological Products
The candidate is an inactivated vaccine that is made of virus particles that are grown in culture and lack disease-producing capability.
Developed by the Wuhan Institute of Biological Products under the China National Pharmaceutical Group, Sinopharm, the vaccine candidate entered Phase 3 clinical trials on July 17, 2020 in Abu Dhabi, UAE. Health authorities in the UAE are allowing up to 15,000 volunteers 18 to 60 years of age with no serious underlying medical issues and without previous COVID-19 infection to take part in the study.
The phase 3 trial of the COVID-19 inactivated vaccine candidate follows two earlier Phase 1 and 2 trials held by Sinopharm. The trials are claimed to have been successful with the vaccine candidate generating high titers of antibodies among participants following two doses of the vaccine.
• Ad5-nCoV from CanSino Biologicals
This is a recombinant novel coronavirus vaccine that incorporates the adenovirus type 5 vector (Ad5) expressing the COVID-19 S-protein. The vaccine candidate is built upon CanSino's adenovirus-based viral vector vaccine technology platform. Results from preclinical animal studies showed that the vaccine candidate induced a strong immune response and demonstrated a good safety profile.
A 20 July study published in The Lancet reported the Phase 2 study (which started 12 April) found the vaccine generated antibody and T-cell responses after a single immunisation in the majority of recipients and appeared to be safe18. Currently the company is in talks with Russia, Brazil, Chile, and Saudi Arabia ready to launch a Phase 3 trial of its experimental COVID-19 vaccine.
On 16 May, Health Canada approved human clinical trials for possible coronavirus vaccine to be conducted in Canada. On 25 June, China's Central Military Commission approved the use of the vaccine by the military for a period of one year.
• INO-4800 from Inovio Pharmaceuticals
A DNA plasmid encoding the S-protein and will be delivered by electroporation into human cells. Once inside the cell, the plasmids begin replicating, producing a specific immune response against COVID-19.
On 30 June, Inovio announced positive interim clinical data of its vaccine candidate from the first two Phase 1 clinical trial cohorts evaluating the safety, tolerability and immunogenicity of INO-4800 in 40 healthy volunteers19. In addition, INO-4800 has been selected to participate in a non-human primate challenge study as part of the US Operation Warp Speed.
Furthermore, INOVIO has expanded its Phase 1 trial to add older participants in additional cohorts and plans to initiate a Phase 2/3 efficacy trial this summer upon regulatory concurrence.
Non-specific COVID-19 vaccines
In addition to COVID-19 targeted vaccines, other vaccines with non-specific effects are undergoing clinical evaluation. The anti-tuberculosis BCG vaccine is being tested for potential protective effect against COVID-19 in two phase 3 trials recruiting about 5,000 healthcare workers in the Netherlands and Australia. The trials are based on the hypothesis that COVID-19 mortality was lower in countries that have routine BCG vaccine administration. However, with an increasing number of cases in countries like South Africa (which do not routinely give the BCG vaccination), this is still under investigation and may not be true.
Numerous other companies and partnerships have plans to develop additional vaccine candidates, which are expected to enter clinical studies over the next couple of months.
Global pharmaceutical collaborations
Several large pharmaceutical companies are collaborating on COVID-19 vaccine work. On March 30, Johnson & Johnson, Janssen Pharmaceutical and the Biomedical Advanced Research and Development Authority (BARDA) (which is part of the US Department of Health and Human Services), announced the selection of a lead COVID-19 vaccine candidate. The company expects to rapidly scale manufacturing capacity with the goal to provide more than one billion doses globally. Johnson & Johnson expects to initiate human clinical studies of its lead vaccine in September 2020 and anticipates the first batches of a vaccine could be available for emergency use in early 2021. This is again a substantially accelerated timeframe compared to the typical vaccine development process20.
Sanofi is engaged in two partnerships: one with BARDA using an existing technology designed to tackle influenza and another with Translate Bio to combine its deep vaccine expertise with Translate Bio’s mRNA platform to discover, design and manufacture several vaccine candidates21.
Pfizer has teamed with BioNTech to co-develop and distribute an mRNA vaccine, similar to Moderna’s. The partners plan to use multiple R&D sites in the US and Germany to accelerate progress of a vaccine that has entered phase 3 testing at the end of July 202022,23.
Alternative immune therapies
Convalescent plasma therapy takes antibody-rich plasma from patients who have recovered COVID-19 and infuses it into individuals diagnosed with the virus. This approach dates back almost 100 years, with some evidence for benefit against rabies, hepatitis B, polio, measles, influenza, Ebola and other pathogens24.
Initial studies on 15 severe COVID-19 patients in China first suggested that convalescent plasma therapy may be a safe and promising therapeutic option25,26. On 13 April, the FDA announced an emergency investigational new drug (eIND) application process to allow physicians to treat patients with serious COVID-19 disease with convalescent plasma collected by a blood centre27.
While outcomes of these studies are optimistic, they represent a small sample and require further investigation. At this time, the use of convalescent plasma is considered an interim approach while vaccines and effective drug therapies are developed. While the concept is simple, numerous steps are involved and the process requires close cooperation between recovered donors, collection centres, treating physicians and receiving patients. Health care administrators and regulators must oversee the safety of each step28. Current estimates suggest that a single donor's plasma could be used to treat only 2-3 recipients. In addition, quantitative serologic assays are not yet widely available to identify convalescent patients with high titer neutralizing antibodies. Finally, we don't know how long this donated immunity would last, what level of protection it offers and who is most eligible to receive it.
Global efforts to develop an effective vaccine in response to the COVID-19 pandemic are unprecedented in terms of scale and speed. First results on the effectiveness for preventing disease from phase 3 clinical trials may be already available in the autumn of this year. That being said,the earliest date one or more vaccines could be available for healthcare staff and high-risk groups is early to mid-2021, with mass vaccination happening as soon as possible afterwards. Despite fast advancing trials and significant funding, success within this timeline cannot be guaranteed, and mass production and distribution will be challenging and time consuming. Another question is whether the broader general public is willing to accept mass vaccination at the earliest opportunity. According to a recent poll in the US, over 60% of Americans think taking a "first-generation" vaccine as soon as it’s available is risky, suggesting that the public remains wary of the vaccine until its safety has been shown29.
The reappearance of a novel coronavirus outbreak has been on the radar of the scientific community for some time. Leading experts agree there were missed opportunities to learn from SARS and MERS to develop a medically proven vaccine predecessor for any type of human coronavirus. Since both these corona epidemics were contained, there was less funding to find a vaccine to fight them. The good news is that coronaviruses tend to mutate less frequently than other RNA viruses, so new therapeutic regimens against other (novel) coronaviruses could increase global resilience against future pandemics.
As the world waits for vaccine trials to yield results, the pandemic will continue to be managed by a combination of non-pharmaceutical means such as social distancing, good hygiene practices and non-vaccine pharmaceutical interventions such as different antiviral and anti-inflammatory agents.
Currently, there are limited drug regimens to treat the infection, which is critical to save lives particularly for those with severe symptoms. It was expected that effective treatments for COVID-19 will arrive sooner than a vaccine, and we discussed the runners and riders in our recent publication on drugs. However, it now seems that one or more successful vaccines are within our grasp. Although the ultimate success of an effective vaccine candidate remains unknown, the leveraging of experimental vaccine platforms and accelerated development timelines that the COVID-19 pandemic has brought are likely here to stay.
Potential vaccines: Seven prominent candidates in clinical trials
Managing editor: Susan Imler, Global L&H Communications
Contributing editor: Simon Woodward, Senior Business Development Manager
- CEPI. CEPI welcomes UK Government’s funding and highlights need for $ 2 billion to develop a vaccine against COVID-19. 1–7 (2020).
- FiercePharma. Bill Gates is able—and willing—to lose big money funding factories for COVID-19 vaccines. (2020).
- FiercePharma. Multiple COVID-19 vaccines? That’s what it could take, GSK CEO Walmsley says.
- HumanVaccinesProject. How soon can we expect a vaccine? (2020).
- European center for disease prevention and control. Coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK – seventh update. 2019, (2020).
- Zhang, B. et al. Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19. medRxiv 2020.03.12.20035048 (2020) doi:10.1101/2020.03.12.20035048.
- Long, Q.-X. et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat. Med. (2020) doi:10.1038/s41591-020-0965-6.
- World Health Organization. Draft of the landscape of COVID-19 candidate vaccines. World Heal. Organ. 4 (2020).
- Holford, N. H. G., Kimko, H. C., Monteleone, J. P. R. & Peck, C. C. Simulation of Clinical Trials. Annu. Rev. Pharmacol. Toxicol. 40, 209–234 (2000).
- Berkley, S. COVID-19 needs a Manhattan Project. Science (80-. ). 367, 1407 (2020).
- Thanh Le, T. et al. The COVID-19 vaccine development landscape. Nat. Rev. Drug Discov. (2020) doi:10.1038/d41573-020-00073-5.
- MilkenInstitute. COVID-19 Treatment and Vaccine Tracker. (2020).
- LSHTM. COVID-19 vaccine development pipeline. (2020).
- Moderna. Moderna Announces Expansion of BARDA Agreement to Support Larger Phase 3 Program for Vaccine (mRNA-1273) Against COVID-19. (2020).
- Zhu, F. C. et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet (2020) doi:10.1016/S0140-6736(20)31605-6.
- Reuters. Brazil health regulator Anvisa allows Chinese COVID-19 vaccine trial. (2020).
- Sinovac. Sinovac Announces Positive Preliminary Results of Phase I/II Clinical Trials for Inactivated Vaccine Candidate Against COVID-19. (2020).
- Folegatti, P. M. et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 1–13 (2020) doi:10.1016/S0140-6736(20)31604-4.
- INOVIO. INOVIO Announces Positive Interim Phase 1 Data For INO-4800 Vaccine for COVID-19. (2020).
- Johnson&Johnson. Johnson & Johnson Announces a Lead Vaccine Candidate for COVID-19; Landmark New Partnership with U.S. Department of Health & Human Services; and Commitment to Supply One Billion Vaccines Worldwide for Emergency Pandemic Use. (2020).
- Sanofi. Sanofi’s Response in the Fight against COVID-19. (2020).
- Pfizer. Pfizer and BioNTech Announce an Agreement with U.S. Government for up to 600 Million Doses of mRNA-based Vaccine Candidate Against SARS-CoV-2. (2020).
- FiercePharma. Pfizer, BioNTech strike COVID-19 deal, commit multiple R&D sites to vaccine development. (2020)
- AmericanSocietyofHematology. COVID-19 and Convalescent Plasma: Frequently Asked Questions. (2020).
- Shen, C. et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA (2020) doi:10.1001/jama.2020.4783.
- Duan, K. et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc. Natl. Acad. Sci. 202004168 (2020) doi:10.1073/pnas.2004168117.
- FDA. Recommendations for Investigational COVID-19 Convalescent Plasma.
- Bloch, E. M. et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J. Clin. Invest. (2020) doi:10.1172/JCI138745.
- IPSOS. Americans adapting as country struggles with coronavirus pandemic. (2020).