Company
Vaccine
Type
Preclinical
Phase I
Phase II
Phase III
AstraZeneca
AZD1222 
or
ChAdOx1 nCoV-19
DNA - Non-replicating viral vector
February 2020
1,090 patient trial initiated in April 2020 with early results published in July
10,260 patient trial initiated in May 2020
30,000 patient trial initiated in August 2020. Announced a combined 70% efficacy for two dosing regimens in November 2020.
BioNTech/Pfizer
BNT162
mRNA - Non-replicating viral vector
March 2020
200 patient trial initiated in April 2020 in Germany and a 7,600 patient trial in the U.S. Results from both trials were reported in July
The German and U.S. trials are Phase I/II
95% efficacy and no safety issues in a 44,000 patients trial announced in November 2020
CanSino Biologics 
Ad5-nCoV
DNA - Non-replicating viral vector
March 2020
108 patient trial initiated in March 2020 with early results published in May 2020 
508 patient trial initiated in April 2020 with results reported in July
 
A 600 patient trial is planned for Canada
Clover Biopharmaceuticals
SCB-2019
Coronavirus-derived protein given with an adjuvant
January 2020
150 patient trial initiated in Australia in June 2020
Planning a Phase IIb/III by the end of 2020
Planning a Phase IIb/III by the end of 2020
CureVac
CVnCoV
mRNA - Non-replicating viral vector
January 2020
Results from a 250 patient trial reported in November 2020
A 700 patient Phase II trial was interred in September 2020
Inovio
INO-4800
DNA plasmid encoding coronavirus spike protein
January 2020
120 patient trial initiated in April 2020
A Phase II/III trial was put on hold in September 2020
Phase II/III trial forecast to begin in July or August 2020
Institute of Medical Biology, Chinese Academy of Medical Sciences
BBIBP-CorV
Inactivated virus
Value
942 patient, Phase I/II trial initiated in April 2020
942 patient, Phase I/II trial initiated in April 2020
Phase II/III trial forecast to begin by the end of 2020
Johnson & Johnson
Ad26.COV2-S
DNA - Non-replicating viral vector
March 2020
1,045 patient, Phase I/IIa trial initiated in July 2020, with early results reported in September 2020
1,045 patient, Phase I/IIa trial initiated in July 2020, with early results reported in September 2020
60,000 patient trial for single dose regimen initiated in Sept. 2020, 2-dose regimen trial initiated in November 2020
Merck
Replicating viral vector
May 2020
A 260 patient, PhaseI/II was initiated in September 2020
A 260 patient, PhaseI/II was initiated in September 2020
Moderna
mRNA-1273
mRNA - Non-replicating viral vector
January 2020
45 patient trial initiated in March 2020 with early results published in July 
600 patient trial completed enrollment in July 2020
30,000 patient trial announced 94.1% effective in 
​November 2020 
Novavax
NVX-CoV2373
or
SARS-CoV-2 rS
Coronavirus-derived protein given with an adjuvant
April 2020
130 patient trial initiated in May 2020
The Phase II part of the 130 patient trial began in July 2020
15,000 patient British initiated in September 2020 and 30,000 U.S. trial planned for December 2020
Sanofi/GSK
Coronavirus-derived protein given with an adjuvant
April 2020
A 440 patient, Phase I/II trial initiated in September 2020
A 440 patient, Phase I/II trial initiated in September 2020
Sinopharm
Inactivated virus
February 2020
A 1,120 patient Phase I/II trial that was initiated in April 2020 reported 100% seroconversion with one dose regimen.
The trial reported initial results in June 2020
A Phase III trial was initiated in the United Arab Emirates in July 2020.
Sinovac 
CoronaVac
Inactivated virus
January 2020
Preliminary results from a 143 patient Phase I trial were announced in April 2020, and no safety issues were found
Preliminary results from a 600 patient Phase I trial were announced in April 2020, and no safety issues were found, and antibodies were formed within 14 days
A 9,000 patient trial in Brazil is planned
Zydus Cadila
ZyCoV-D
DNA plasmid encoding coronavirus spike protein
Preliminary results from a Phase I trial were announced in August 2020, and no safety issues were found
A 1,000 patient trial was initiated in August 2020
Value
Gamaleya Research Institute
Sputnik V
DNA - Non-replicating viral vector
Value
Two Phase I/II studies demonstrated production of antibodies
Two Phase I/II studies demonstrated production of antibodies
The 40,000 patient Phase III RESIST trial was initiated in September 2020, interim data suggested 91.4% efficacy
Vaxart
VXA-CoV2-1 
DNA - Non-replicating viral vector
A 48 patient, Phase I trial initiated in October 2020
Value
Medicago
​CoVLP
Virus like particle
Results form a Phase I  trial became available in November 2020
A 30,000 patient, Phase II/III trial is be initiated at the end of 2020
A 30,000 patient, Phase II/III trial is be initiated at the end of 2020
General Information on COVID-19 Vaccine Development
  1. In April 2020, NIH formed the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership with HHS, FDA, CDC, EMA and AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Evotec, GlaxoSmithKline, J&J, KSQ Therapeutics, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda and Vir. ACTIV will coordinate and prioritize trials to optimize vaccine and treatment development for COVID-19 through a steering committee of representatives of members.
  2. Experts have estimated that initial supplies of a COVID-19 vaccine will only allow immunization of health care employees. A larger supply that will allow mass immunization may not be available until spring or summer 2021.
  3. A description of ACTIV’s strategy to develop successful vaccines was published by Anthony Fauci, MD, along with other government physicians and academic researchers. The report describes approaches to develop vaccines and scale them up to meet worldwide needs. The benefits and challenges of each type of vaccine is discussed along with the need to have multiple vaccines.
  4. Operation Warp Speed, a U.S. program designed to rapidly accelerate the development and availability of a vaccine for COVID-19, has chosen five vaccines they consider having the best chance to succeed. The vaccines chosen are being developed by Moderna (currently in Phase II), AstraZeneca (currently Phase II), Pfizer (currently in two Phase I/II trials) and vaccines in pre-clinical development from Johnson & Johnson and Merck.
  5. NIAID has established the COVID-19 Prevention Trials Network (COVPN), as part of Operation Warp Speed. The Network is designed to accelerate the development of vaccines and monoclonal antibodies for the prevention of COVID-19. COVPN is composed of four clinical trial networks, three that had focused on HIV/AIDS and a fourth targeting the development of vaccines and treatments for infectious diseases.
  6. ​In order to qualify for an Emergency Use Authorization, the vaccine should have at least 2-months of data from a Phase III trial demonstrating at least 50% efficacy. The FDA plans to post their reviews and data supporting an Emergency Use Authorization for COVID-19 vaccines. The FDA is working on a meeting during second week of December for its vaccines advisory committee to discuss COVID-19 vaccines from Pfizer-BioNTech and Moderna. Peter Marks, the head of the FDA’s Center for Biologics Evaluation and Research said the FDA review may takes weeks
  7. The FDA’s Advisory Committee on Immunization Practices recommended that health care providers and long-term care residents be the first to be immunized for COVID-19. Health care providers includes those who work in hospitals, outpatient clinics, long-term care facilities, home health, public health, emergency medical services and pharmacies.
The journal Nature provided a graphical description of the different types of methods to create a vaccine that are currently being used to work on a vaccine for COVID-19. Ultimately each vaccine elicits an immune response that leads to the production of antibodies.
  • A whole virus vaccine uses a weakened or inactivated virus
  • Viral vectors use a genetically modified virus to produce a virus protein that causes the immune response. The immune response may be weakened if a common virus is used which has a high degree of immunity in the community. As an example, it is speculated that if a modified adenovirus is used, a booster immunization may be required to maintain immunity.
  • Nucleic acid vaccines use DNA or RNA to causes a cell to produce a protein that causes an immune response. Since the full virus is not produced, no infection develops. No approved vaccine currently uses this technology. While mRNA and DNA vaccines can be designed, manufactured and tested faster than typical vaccines, the vaccine design have not been proven to be efficacious or safe.
  • Protein-based vaccines use a protein from the virus that will cause an immune response without infection. This type of vaccine requires an adjuvant to stimulate the immune response. No protein-based vaccine has been tested in a human.
  • Virus-like particles are empty virus shells that mimic the virus structure, but do not have the genetic material to cause an infection. These vaccines can stimulate a strong immune response but are harder to manufacture.
Some of the more advanced vaccine projects include:

​AstraZeneca and the University of Oxford are developing a vaccine (AZD1222) created by the University of Oxford that uses a non-replicating chimpanzee adenovirus, that is not infectious to humans. The adenovirus is genetically modified to contain COVID-19 spike proteins. AstraZeneca agreed to sell its COVID-19 vaccine near cost and may be charging as low as $3 per dose. AstraZeneca has agreements with Brazil, Argentina and Mexico to manufacturer AZD1222 to supply patients in Central and South America. The EMA has started a rolling review of AstraZeneca’s COVID-19 vaccine with early non-clinical data, while the FDA still has a hold in place for the U.S. Phase III trial.
  1. AZD1222 is also listed as ChAdOx1 nCoV-19
  2. AstraZeneca is working with contract research organization IQVIA to accelerate enrollment and completion of a Phase III trial for AZD1222 as part of Operation Warp Speed.
  3. In a 56-day, 1,077 patient, Phase I/II, British trial (NCT04324606), neutralizing antibody levels after a single dose of AstraZeneca’s and the University of Oxford’s AZD1222 vaccine, peaked at 28-days and remained elevated through day 56 with 90% of participants developing antibodies. A booster dose was given four weeks later to 10 patients and resulted in higher antibody levels. Many patients developed systemic reactions (e.g., chills, fever) compared to meningococcal conjugate vaccine, but the reactions were reduced with acetaminophen. 
  4. AstraZeneca initiated a 30,000 patient, Phase III, U.S. trial (NCT04516746) in August 2020, to evaluate the safety, efficacy and immunogenicity of AZD1222. The trial was funded through a $1 billion grant from BARDA that also covers the rights to 300 million doses of the AZD1222 vaccine that will start being delivered in October. AstraZeneca paused all clinical trials for its COVID-19 vaccine (AZD1222), on 9/6/2020, due an adverse event in one patient. The patient suffered neurological symptoms consistent with transverse myelitis. The UK Medicines Health Regulatory Authority investigated the occurrence as a potential safety problem and allowed the trial to continue on 9/12/2020. The FDA allowed the Phase III trial for AstraZeneca’s coronavirus vaccine, AZD1222, to resume in the US, on 10/23/2020 after an FDA review of all safety data concluded the vaccine was safe.
  5. Results from the 500 patient, Phase II portion of a 12,390 patient, Phase II/III trial found that AZ’s AZD1222 elicited similar antibody titers in all age groups. The vaccine was well tolerated and older patients had fewer adverse reaction than younger patients.
  6. An interim analysis of data from 11,636 patients participating in four trials (NCT04324606, (NCT04400838, NCT04444674, ISRCTN89951424 )evaluating AstraZeneca’s COVID-19 vaccine (AZD1222 or ChAdOx1 nCoV-19) found the average efficacy for two dosing regimens of the vaccine to be 70% in preventing COVID-19. Giving a half dose as the first immunization and a full dose four weeks later resulted in 90% efficacy (n=2,741), while giving a full dose at both immunizations resulted in 62% efficacy (n=8,895). No safety issues were found. The vaccine can be stored, transported and handled at 2-8 degrees Celsius for at least six months. 
  7. AstraZeneca is designing a new trial to evaluate the efficacy of the half-strength initial dose/full strength second dose regimen that demonstrated 90% efficacy in a small subpopulation in a 22,690, Phase III trial.  
  8. The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has issued an emergency authorization for AstraZeneca’s COVID-19 vaccine. Immunization with the vaccine is expected to begin in early January 2021. AZ’s vaccine will probably not be available in the U.S. until April 2021.
BioNTech – is developing a messenger RNA (mRNA) vaccine (BNT162) in partnership with Pfizer and Fosun Pharma. BioNTech will manufacture the vaccine in Germany and Pfizer will manufacture the vaccine at three sites in the US and one in Belgium. Pfizer is not relying on government funding for development and says it can move faster with self-funding. HHS and the BARDA awarded Pfizer and BioNTech $1.95 billion for the first 100 million doses of their experimental COVID-19 vaccine as part of operation Warp Speed. The U.S. government also has an option for an additional 500 million doses. Pfizer plans to price the two dose COVID-19 vaccine regimen at a minimum of $19.50 per dose or $39 for the two dose course of immunizations for the additional 500 million doses the U.S. can purchase under an Agreement. The price will be the same for other developed countries that make the same volume commitment. 
  1. Two doses of BNT162 are given 21 days apart.
  2. On 12/11/2020, the FDA granted an Emergency Use Authorization (EUA) for Pfizer-BioNTech’s COVID‐19 Vaccine for the prevention of COVID-19 for individuals 16 years of age and older. Vaccine Fact Sheets are available for Healthcare Providers and Vaccine Recipients/Caregivers. The CDC's Advisory Committee on Immunization Practices (ACIP) voted 11-0, with three recusals to recommend use of Pfizer-BioNTech’s vaccine on 12/12/2020. ACIP also had a unanimous vote to include the vaccine in 2021 immunization schedules. The committee noted there are little data on vaccine outcomes in patients who are pregnant, lactating, immunocompromised, or have severe allergies.  The CDC will offer guidance for use of the vaccine in these groups before the end of the year. The CDC officially accepted ACIP’s recommendation to use Pfizer’s COVID-19 vaccine in people 16 and older, the same day.
  3. An FDA review of clinical data for Pfizer and BioNTech’s COVID-19 vaccine found evidence supported 95% efficacy and no major safety concerns. On 12/10.2020, the FDA’s Vaccines and Related Biological Products Advisory Committee voted 17 to 4, with one abstention to recommend an emergency use authorization for BNT162b2 as prophylaxis for COVID-19 infections for patients 16 years and older. Pfizer and BioNTech will monitor for anaphylactic reactions as part of their pharmacovigilance plan after two patients in the U.K. developed reactions after receiving the vaccine.
  4. In a 195 patient, Phase I trial (NCT04368728), two vaccine candidates (BNT162b1 and BNT162b2) were tested in healthy adults. Patients that received BNT162b2 had a lower incidence and severity of systemic reactions than BNT162b1. No safety issues were identified, but most participants reported mild to moderate injection site pain. Tiredness, headaches and fever was reported after the second dose. Both vaccines elicited antibody levels one-month after a second dose of vaccine that were greater than levels seen in a group of recovered COVID-19 patients. 
  5. In a 60 patient, open-label, dose-ranging, Phase I/II, German trial (NCT04380701), participants were given two doses of Pfizer’s and BioNTech’s BNT162, separated by three weeks. The vaccine elicited a dose-dependent antibody response with the 50 mcg dose resulting in neutralizing antibody levels that were three times those in recovered COVID-19 patients. The article also describes the T-cell responses in 36 patients with both CD4 cells (34 patients) and CD8 cells (29 patients).
  6. In the Pfizer funded, 43,0448 patient, Phase II/III trial (NCT04368728) BNT162b2 was administered as two 30 mcg immunizations given 21-days apart. BNT162b2 efficacy was found to be 95% (8 cases of COVID-19 vs 162 cases), 28 days after the first dose and 7 days after the second dose. Protection for COVID-19, began around 12 days after the first dose, with 52% efficacy between the first and second doses. Efficacy was consistent across age, gender, race and ethnicity demographics. The most common ADR were mild-to-moderate pain at the injection site, fatigue, and headache. There were few serious ADR and the incidence was similar to placebo. After the second dose, fever developed in 16% of younger patients and 11% of older patients.
  7. In an unpublished and unedited report, researchers describe how antibodies in serum from 20 people, who had received two doses of the Pfizer-BioNTech COVID-19 vaccine, neutralized SARS-CoV-2 with and without the mutation (N501Y) with similar efficacy. The N501Y mutation has been identified as causing a faster spread of the disease in the U.K. It has also been identified in the U.S.
  8. Pfizer and BioNtech will have 50 million vaccine doses available in 2020 and up to 1.3 billion doses in 2021. BioNTech announced that the COVID-19 vaccine it is developing with Pfizer, BNT162b2, can be stored for up to five-days at 2 to 8 C. The shipping container will keep the vaccine viable for up to ten days if stored at 15 to 25 C without opening and up to 15 days if opened and then re-iced with dry ice. The vaccine is stable for up to six months at -70 C. 
  9. The FDA has advised it is acceptable to use each additional full dose in the vials.  But partial doses from different vials, should not be combined for a full dose, since the vials are preservative free.
  10. ​The American College of Obstetricians and Gynecologists (ACOG) recommends the Pfizer-BioNTech COVID-19 vaccine should not be withheld from pregnant or lactating women who meet criteria for vaccination based on ACIP-recommended priority groups. A discussion with the patient of the vaccine should include the potential for adverse effects, hand washing and wearing a mask. Patients should be educated that an mRNA vaccine is not a live virus vaccine and no adjuvant is used in the Pfizer-BioNTech COVID-19 vaccine. The mRNA vaccines do not enter the nucleus and do not alter human DNA in vaccine recipients, so these types of vaccines cannot cause any genetic changes. The CDC also discusses mRNA vaccines on a dedicated web page. ACOG recommends the patient’s decision on whether to receive the vaccine should be supported.
  11. The CDC has provided interim clinical considerations for the Pfizer-BioNTech and Moderna COVID-19 vaccines. 
  • Delay vaccination of patients with an acute COVID-9 infection until the patient has recovered. Immunization may be delayed for up to 90 days.
  • Patients that have received convalescent or COVID-19 antibodies should have their immunization delayed for 90 days.
  • Immunocompromised, autoimmune or pregnant patients with no contraindications, may receive the vaccine. Potential risks should be discussed with the patient, such as the unknown vaccine safety profile and effectiveness in immunocompromised populations, as well as the potential for reduced immune responses.
  • Patients with a history of anaphylactic reactions should be observed for 30 minutes after vaccination
  • Patients with a history of allergic, but not anaphylactic reactions should be observed for 15 minutes after vaccination
  • No other vaccines should be given within two weeks of the Pfizer-BioNTech vaccine.
  • The Pfizer-BioNTech and Moderna vaccines cannot be used interchangeably and the series should be completed with the vaccine the patients originally received. However if two doses of different products are inadvertently administered, no additional dose should be given of either vaccine.
  • Patients with a history of Guillain-Barré syndrome or Bell’s palsy may receive the vaccine.
CanSino Biologics – is developing the non-replicating adenovirus type-5 (Ad5) viral vector DNA virus, Ad5-nCoV. The Chinese military approved the use of Ad5-nCoV in soldiers based on results from the Phase I and II trials. 
  1. The vaccine is given as single Intramuscular Injection. A Canadian trial will also evaluate a second dose given at 56 days.
  2. In a 108 patient, Phase I, dose escalation, open-label trial, (ChiCTR2000030906) healthy Chinese patients developed antibodies after receiving a single immunization with CanSino’s Ad5-nCoV, but patients with high Ad5 antibody titers produced lower levels of COVID-19 antibodies. Most patients experienced a mild to moderate adverse event with the most common being injection site pain, fever, fatigue, headache and muscle pain. Because the vaccine is Ad5 vectored and most adults have immunity to Ad5, the efficacy in older patients may not be as strong as in younger patients. Based on preliminary safety data from the first 14-days of the Phase I trial, CanoSino initiated a 500 patient, Phase II trial for Ad5-nCoV in May using the low and middle doses of the vaccine.
  3. In a 508 patient, dose-ranging, Phase II, Chinese trial (NCT04341389), a single dose of CanSino’s COVID-19 vaccine resulted in seroconversion in more than 96% of participants; 85% produced neutralizing antibodies and 90% had T-cell response. As was seen in the Phase I trial, participants that were 55 or older and those with adenovirus immunity had lower humoral responses, but this did affect T-cell responses. The most frequent systemic reactions were fatigue, fever and headache.
  4. CanSino has canceled a Phase II/III trial in Canada, after the Chinese government refused to allow the company to ship the vaccine to Canada for the trial. The CanSino COVID-19 vaccine, Ad5-nCoV, is based on technology developed by Canadian firm NRC. 
  5. ​CanSino plans to initiate a 5,000 patient, Phase III trial in Saudi Arabia.
  6. CanSino is evaluating a two-dose regimen of Ad5-nCoV in a 168 patient, Phase I trial (NCT04552366) in China.
Clover Biopharmaceuticals is developing SCB-2019, a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine. SCB-2019 is a Coronavirus-derived protein given with an adjuvant. 
  1. Clover announced that in a 150 patient, Phase I Australian trial (NCT04405908), Clover’s protein-based COVID-19 vaccine candidate combined with GSK’s vaccine adjuvant, ASO3 induced antibodies in all participants, while the vaccine adjuvanted with Dynavax’s vaccine adjuvant, CpG 1018 induced antibodies in younger and middle aged adults, but in 88% (7/8) of elderly patients.
  2. Clover announced that in a 150 patient, Phase I Australian trial (NCT04405908), Clover’s protein-based COVID-19 vaccine candidate combined with GSK’s vaccine adjuvant, ASO3 induced antibodies in all participants, while the vaccine adjuvanted with Dynavax’s vaccine adjuvant, CpG 1018 induced antibodies in 100% of younger and middle aged adults, but in 88% (7/8) of elderly patients.
  3. Clover plans a Phase IIb/III to evaluate the safety and efficacy of SCB-2019 in combination with GSK’s vaccine adjuvant, ASO3, by the end of 2020. 
  4. Clover plans a Phase IIb/III to evaluate the safety and efficacy of SCB-2019 in combination with Dynavax’s vaccine adjuvant, CpG 1018, in the first half of 2021. CpG 1018 is used in Dynavax’s HEPLISAV-B (hepatitis-B) vaccine.
CureVac - is developing CVnCoV, an mRNA vaccine formulated with lipid nanoparticles. The Coalition for Epidemic Preparedness Innovations (CEPI) has provided funding to CureVac and Germany invested $337 million in CureVac to support development and manufacture of a COVID-19 vaccine. CureVac has signed an agreement with Bayer to help develop, distribute and market its COVID-19 vaccine candidate CVnCoV.
  1. An unpublished report describes interim data from a 248 patient, Phase I dose ranging trial (NCT04449276), where two 12 mcg doses of CureVac’s COVID-19 vaccine, CVnCoV, elicited antibody levels similar to levels seen in a group of recovered COVID-19 patients. In the Phase I trial, healthy patients were randomized to doses of 2, 4, 6, 8 and 12 mcg on days 1 and 29. The 12 mcg dose was chosen for future trials. Most adverse events were mild or moderate. The most common were headache and fatigue, myalgia, chills and fever.
  2. CureVac is evaluating CVnCoV in a 700 patient, Phase II dose-ranging trial (NCT04515147) in Peru and Panama.
  3. Curevac is evaluating CVnCoV for the prevention of COVID-19 in the 36,500 patient, Phase IIb/III, HERALD trial (NCT04652102) in Europe and Latin America.
  4. Curevac is evaluating the safety, reactogenicity and antibody response of CVnCoV in a 2,520 patient, Phase III, trial (NCT04674189) in German adult healthcare providers.
Gamaleya Research Institute is developing Gam-COVID-Vac (Sputnik V), a non-replicating adenovirus type-5 (Ad5) viral vector DNA virus. Russia approved the COVID-19 vaccine after limited Phase I testing. 
  1. Gam-COVID-Vac is being developed as both a frozen and lyophilized form. The lyophilized vaccine does not require freezing, which may make it easier to distribute in developing nations.
  2. Two 38 patient, Phase I/II clinical trials (NCT04436471 and NCT04437875) demonstrated that antibodies were produced. Two doses of Gam-COVID-Vac were given 21 days apart in the Phase II trial.
  3. Gamaleya is evaluating Gam-COVID-Vac in the prevention of COVID-19 in the 40,000 patient Phase III (RESIST) trial (NCT04530396). Two doses of Gam-COVID-Vac will be given 21 days apart in the trial. The Russian National Research Center for Epidemiology and Microbiology announced results from a second interim analysis of the Sputnik V vaccine, where efficacy was estimated to be 91.4%, 28 days after the first dose and seven days after the second dose, based on the distribution of 39 cases of COVID-19 among 18,794 patients. (Note: Pfizer based their 95% efficacy on 170 cases distributed among 41,135 patients and Moderna reported 94.1% efficacy after 196 cases of COVID-19 occurred in over 30,000 patients). 
  4. The Russian sovereign wealth fund announced the COVID-19 vaccine, Sputnik V, will be available internationally beginning in January 2021 as a two-dose regimen priced less than $20.
Inovio - is developing a DNA vaccine (INO-4800). Inovio has potential supply issues. The company can only produce 1 million doses by the end of 2020. Inovio has contracted Ology Bioservices and Richter-Helm BioLogics to add manufacturing capacity but is suing VGXI and GeneOne Life Science, its current plasmids suppliers, to transfer the technology to Ology and Richter-Helm.
  1. INO-4800 is administered by electroporation, where a small electrical pulse opens small pores in cells to allow the DNA to enter. Two doses are given four weeks apart.
  2. Inovio initiated a 40 patient, Phase I trial in April (NCT04336410). Patients received two doses of INO-4800 4-weeks apart. In June, Inovio announced the vaccine elicited antibodies in 94% of patients, 6-weeks after the second immunization, and no safety issues were identified.
  3. The FDA placed a hold on a Phase II/III trial evaluating Inovio’s COVID-19 vaccine, INO-4800, due to questions regarding the vaccine and the Cellectra 2000 delivery device  used in the trial
Institute of Medical Biology and the Chinese Academy of Medical Sciences are developing the inactivated virus vaccine BBIBP-CorV.
  1. Animal studies demonstrated development of antibodies.
  2. A dose ranging, 942 patient, Phase I/II trial was initiated in May (NCT04412538)
Johnson and Johnson – is developing a non-replicating viral vector vaccine and will use J&J’s AdVac and PER.C6 technologies developed in the Ebola and HIV vaccine programs to allow rapid upscale production of its COVID-19 vaccine Ad26.COV2-S. J&J forecasts that it will be able to produce 1 billion doses by the beginning of 2021. The Departments of Defense and Health and Human Services, as part of Operation Warp Speed, have awarded Johnson & Johnson $1 billion for the first 100 million doses ($10 per dose) of its experimental COVID-19 vaccine. The supply will be used for clinical trials or provided, at no charge, through a U.S. vaccination program. The U.S. government also has an option for an additional 200 million doses.
  1. J&J began development work on a single dose vaccine, Ad26.COV2-S in March 2020.
  2. In a 805 patient, Phase I/IIa trial (NCT04436276), JNJ’s COVID-19 vaccine, Ad26.COV2.S, elicited neutralizing antibodies in two cohorts of patients (18-55 and 65 or older). 29 days after the first dose, neutralizing-antibodies were produced in 99% of patients in the younger cohort and 96% of patients in the older cohort. Antibody titers continued to increase at day 57. A higher dose of the vaccine elicited more antibodies than the lower dose. Some patients received a second dose of the vaccine, which resulted in even higher antibody levels. Longer term data comparing one-dose and two-dose regimens will be reported in the future. The most frequent adverse events were injection site pain, fatigue, headache and myalgia. Adverse events were less common in older patients than younger patients.
  3. Additional trials include a Phase I study in Japan, and a Phase II study in the Netherlands, Spain and Germany.
  4. J&J initiated the 60,000 patient, Phase III, ENSEMBLE trial (NCT04505722) to evaluate a single dose of  JNJ-78436735 for the prevention of COVID-19 in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa and the United States. J&J temporarily paused the Phase III ENSEMBLE trial in October 2020, due to an unexplained illness in a study participant. Johnson & Johnson resumed the Phase III ENSEMBLE trial in October 2020, after a Data Safety and Monitoring Board review found no evidence that COVID-19 vaccine candidate, Ad26.COV2-S, caused a serious medical event experienced by one study participant.  J&J and Operation Warp Speed are reducing the size of the ENSEMBLE trial due to the surge in COVID-19 cases that allowing accumulation of at least 154 cases of severe or moderate COVID-19 infection more quickly. J&J announced completion of enrollment in the 45,000 patient, Phase III, ENSEMBLE trial in mid-December 2020. J&J estimates interim data to be available at the end of January 2021 and a request for an Emergency Use Authorization in February 2021.
  5. Johnson and Johnson is initiating a 30,000 patient, Phase III, ENSEMBLE 2 trial (NCT04614948), to evaluate a two doses of JNJ-78436735 given 57 days apart compared to placebo. BARDA is giving J&J an additional $454 million and J&J is providing $604 million, for the ENSEMBLE Phase III program. The Phase III, ENSEMBLE trial (NCT04505722) is evaluating a single dose of JNJ-78436735 in a 60,000 patient trial.
Medicago - is developing a virus-like particle vaccine (CoVLP). The virus-like particles are created in genetically modified plant cells. Medicago has signed an agreement to provide 76 million doses to Canada.
  1. Two doses of CoVLP are given with GSK’s vaccine adjuvant 21 days apart.
  2. In an unpublished report of a 180 patient, Phase I, dose-ranging trial, all patients given CoVLP with GSK’s adjuvant elicited neutralizing antibodies after a second dose of the vaccine. Based on results, the lowest dose (3.75 mcg) was chosen for a Phase III trial.
  3. Medicago will evaluate the safety and efficacy of CoVLP in a 30,000 patient, Phase II/III trial. 
Merck – is working on two replicating viral vector vaccines
  1. Merck bought Themis and is working on a vaccine that will use a DNA sequence for viral antigen delivered via the measles virus. This vaccine uses the same technology used in Merck’s investigational chikungunya vaccine.
  2. Merck initiated a 260 patient, Phase I/II trial (NCT04498247) to evaluate the safety, tolerability and immunogenicity of its COVID-19 vaccine, V591, in September 2020.
  3. Merck is working with IAVI to develop a DNA sequence for viral antigen delivered via vesicular stomatitis virus. The technology is the same used in Merck’s Ebola vaccine. A Phase I trial is projected to start in the second half of 2020.
Moderna – is developing the messenger RNA (mRNA) vaccine mRNA-1273. NIH and the Coalition for Epidemic Preparedness Innovations (CEPI) are providing funding to Moderna to develop the vaccine. Moderna hopes to file a BLA for mRNA-1273 in early 2021. Moderna has entered an agreement with Swiss pharmaceutical company Lonzo to help manufacture mRNA-1273. Lonzo will begin manufacturing the vaccine this summer at a U.S. facility and will expand manufacturing to other locations in order to scale up production. Moderna forecasts that 500,000 doses will be available by the end of 2020 and up to 1 billion doses in 2021. Moderna signed an agreement with Catalent to increase capacity for filling vials and packaging doses. Moderna has signed some early vaccine supply deals, pricing their COVID-19 vaccine at $32 to $37 per dose or $64 to $74 per two dose regimen. These early deals were for smaller supplies, so larger orders could have a lower cost per dose, but Moderna has not specified the price. HHS and the BARDA awarded Moderna $1.5 billion for the first 100 million doses ($15 per dose) of its experimental COVID-19 vaccine, mRNA-1273, as part of operation Warp Speed. The U.S. has an option to acquire additional 400 million doses. Should the vaccine be approved, the Federal supply will be provided at no charge, but health care providers can charge for administration. The $1.5 billion is in addition to the $955 million provided to Moderna for vaccine development and manufacturing scale-up.
  1. The vaccine is given as two Intramuscular Injection given 28 days apart.
  2. An FDA review of clinical data for Moderna’s COVID-19 vaccine found evidence supporting 94.1% efficacy and no major safety concerns. An age specific breakdown of efficacy found the vaccine to be 95.6% efficacious in patients under 65 and 84.6% efficacious in those 65 and older. Efficacy was consistent across race and ethnicity demographics. The most common ADR were mild-to-moderate pain at the injection site, fatigue, headache, muscle pain, joint pain and chills. Three vaccine recipients and one placebo recipient experienced Bell’s palsy, so the FDA has recommended ongoing monitoring for Bell's once widespread vaccination begins. On 12/17/2020, the FDA’s Vaccines and Related Biological Products Advisory Committee voted 20-0, with one abstention to recommend an emergency use authorization for mRNA-1273 as prophylaxis for COVID-19 infections for patients 18 years and older. On 12/18/2020, the FDA granted an Emergency Use Authorization (EUA) for Moderna’s COVID‐19 Vaccine for the prevention of COVID-19 for individuals 18 years of age and older. Vaccine Fact Sheets are available for Healthcare Providers and Vaccine Recipients/Caregivers. The CDC's Advisory Committee on Immunization Practices (ACIP) voted 11-0, with three recusals to recommend use of Moderna’s vaccine on 12/19/2020. The FDA approved use of any full extra doses contained in the vials of the Moderna COVID-19 vaccine.  Because the vaccine does not contain preservative, the FDA advises not to pool excess vaccine from multiple vials to create one dose
  3. Moderna announced that mRNA-1273 is stable for 30 days at 2 to 8 C and for six-months at -20 C. This will make the vaccine easier to ship and use in pharmacies, clinics and small hospitals.
  4. In a 45 patient, Phase I, NIAID trial (NCT04283461), the antibody level increased with higher doses of Moderna’s mRNA-1273 (25, 100 and 250 mcg). Antibody titers further increased with a booster dose at 1-month. All doses produced serum-neutralizing activity that were similar to the levels seen in recovered patients. The incidence of adverse effects was higher after the second vaccination, especially with the 250 mcg dose. In a report on older patients in the trial, the mRNA-1273 antibody titers in patients > 56 that were similar to those seen in younger patients, but higher is patients 56-70 than those 71 and older  Antibody titers further increased with a booster dose at 1-month. As with the trial of younger patients, serum-neutralizing activity was similar to the levels seen in recovered patients. Adverse events were primarily mild to moderate (e.g., chills, fatigue) and occurred more frequently after the second vaccination.
  5. Moderna completed enrollment in a 600 patient, Phase II trial (NCT04405076) in early July. Patients were given a low dose (50 micrograms), high dose (100 micrograms) or placebo. Half of the patients enrolled in the trial are older than 55. 
  6. In the NIAID funded, 30,420 patient, Phase III, COVE trial (NCT04470427), mRNA-1273 administered as two 100 mcg immunizations given 28 days apart resulted in 94.1% efficacy based on 196 cases of COVID-19 that developed in the study population. 24.8% of the study population was over the age of 65 and 16.7% were under 65 with increased risk for severe COVID-19 due to co-morbidities. The study population also included 10.2% who identified as Black or African American and 20.5% Hispanic or Latino. The most common adverse effects were injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site. There was a slight increase in frequency and severity of adverse effects after the second immunization. 
  7. The CDC has provided interim clinical considerations for the Pfizer-BioNTech and Moderna COVID-19 vaccines. 
  • Delay vaccination of patients with an acute COVID-9 infection until the patient has recovered. Immunization may be delayed for up to 90 days.
  • Patients that have received convalescent or COVID-19 antibodies should have their immunization delayed for 90 days.
  • Immunocompromised, autoimmune or pregnant patients with no contraindications, may receive the vaccine. Potential risks should be discussed with the patient, such as the unknown vaccine safety profile and effectiveness in immunocompromised populations, as well as the potential for reduced immune responses.
  • Patients with a history of anaphylactic reactions should be observed for 30 minutes after vaccination
  • Patients with a history of allergic, but not anaphylactic reactions should be observed for 15 minutes after vaccination
  • No other vaccines should be given within two weeks of the Pfizer-BioNTech vaccine.
  • The Pfizer-BioNTech and Moderna vaccines cannot be used interchangeably and the series should be completed with the vaccine the patients originally received. However if two doses of different products are inadvertently administered, no additional dose should be given of either vaccine.
  • Patients with a history of Guillain-Barré syndrome or Bell’s palsy may receive the vaccine.
Novavax – is developing a recombinant protein nanoparticle vaccine that will contain coronavirus spike (S) protein antigens and Novavax’s saponin-based Matrix-M adjuvant to enhance immunogenicity. Novax has a $384 million grant from the Coalition for Epidemic Preparedness Innovations (CEPI) and a $60 million grant from the U.S. Department of Defense. Novavax purchased Praha Vaccines and its Czech Republic vaccine factory. That plant has an annual capacity of one billion doses per year. Novavax signed an agreement with Fujifilm Diosynth Biotechnologies to manufacture its COVID-19 vaccine, NVX-CoV2373, in North Carolina and Texas. Novavax also signed contracts with AGC Biologics and PolyPeptide to help produce its Matrix-M adjuvant. In addition Novavax has an agreement with Serum Institute of India to manufacture the antigen component of NVX‑CoV2373. The company now has six antigen production sites and three adjuvant manufacturing sites. This gives Novavax the capacity to produce two billion doses of the NVX-CoV2373 annually beginning in 2021.
  1. NVX-CoV2373 is also listed as SARS-CoV-2 rS.
  2. The FDA granted Novavax’s COVID-19 vaccine, NVX-CoV2373, a Fast Track Designation for the prevention of COVID-19.
  3. Novavax has received $1.6 billion grant from the Departments of Defense and Health and Human Services as part of Operation Warp Speed. The grant will cover the manufacture of 100 million doses of its COVID-19 vaccine, NVX-CoV2373, and a Phase III trial. Dose manufacturing and clinical testing will occur in parallel.
  4. Novavax signed an agreement with Fujufilm Diosynth Biotechnologies to manufacture the Novavax COVID-19 vaccine NVX-CoV2373.
  5. In a 131 patient, Phase I trial (NCT04368988), the antibody level increased with all doses of Novavax’s NVX-CoV2373 COVID-19 vaccine with or without the Matrix-M adjuvant. Either formulation of the vaccine with adjuvant induced neutralizing antibody levels greater than what is seen in recovered COVID-19 patients. The trial was sponsored by the Coalition for Epidemic Preparedness Innovations and performed in Australia. 
  6. NIH announced the initiation of a 30,000 patient, Phase III, trial (NCT04611802) to evaluate the safety and efficacy of NVX-CoV2373, a COVID-19 vaccine from Novavax. Two vaccinations will be given 21-days apart. Due to difficulties in scaling up vaccine manufacturing, the initiation of the trial was delayed twice. 
  7. Novavax initiated a 15,000 patient, Phase III trial to evaluate two doses of NVX-CoV2373 given 21-days apart for the prevention of COVID-19 in the United Kingdom (NCT04583995). At least 25% of trial participants will be 65 or older. Novavax completed enrollment in November 2020 and expects the first interim data to be reported in 1Q21. 
  8. Novavax is evaluating two doses of NVX-CoV2373 given 21-days apart for the prevention of COVID-19 in South Africa in a 4,422 patient, Phase IIb trial (NCT04533399). The trial includes 245 medically stable, HIV-positive participants
Sanofi and GSK – Sanofi and GlaxoSmithKline have agreed to work together to develop a vaccine for COVID-19. The companies will use Sanofi’s S-protein COVID-19 antigen based on the company’s recombinant DNA technology in combination with GSK’s pandemic adjuvant technology. The recombinant DNA platform is the same one used to create the quadrivalent influenza vaccine FluBlok. GSK’s vaccine adjuvant reduces the amount of antigen required for a dose enabling a quicker way to scale up production. Both companies have the capacity to manufacture vaccines on a global scale. Sanofi and GlaxoSmithKline received a $2.1 billion grant from Operation Warp Speed to fund clinical trials, scale up manufacturing, and deliver 100 million doses of their COVID-19 vaccine to the U.S. The deal also includes an option for an additional 500 million doses.
  1. Sanofi and GSK announced a delay in their COVID-19 vaccine development program when an interim analysis of a 441 patient, Phase I/II trial (NCT04537208) found the vaccine to elicit antibodies comparable to convalescent plasma in patients 18 to 49, but the response in older patients was insufficient.
  2. Sanofi and GSK plan to initiate a Phase IIb trial in February 2021 to test a vaccine formulation with a higher antigen content. The Sanofi and GSK vaccine will be compared to a vaccine that has received an EUA. If the trial is successful, a Phase III is projected to be initiated in 2Q21.
  3. Sanofi has signed an agreement with Translate Bio for an mRNA vaccine. A Phase I trial is expected to begin by the end of 2020.
Sinopharm is developing an inactivated virus vaccine. Sinopharm is a Chinese government-controlled company. Sinopharm has priced its COVID-19 vaccine at $145 for two doses. 
  1. Two doses given 28-days apart
  2. Sinopharm is offering the investigational vaccine to employees of large state-owned companies who intend to travel overseas
  3. A dose ranging Phase I/II trial was initiated in April (ChiCTR2000032459). Sinopharm announced that in a 1,120 patient, Phase I/II, dose ranging trial, patients received two injections of placebo or vaccine at low, middle or high dosing strengths. The second immunization was given at 14 days, 21 days or 28 days. The middle dose appeared to elicit the highest seroconversion rate with 14-day and 21-day schedules eliciting a 97.6% rate, and a 100% rate with the 28-day schedule.
  4. In a 96 patient, Phase I, dose ranging trial, (ChiCTR2000031809) patients received three immunization of adjuvant alone or Sinopharm’s COVID-19 vaccine at low, middle or high strengths (2.5 mcg, 5 mcg or 10 mcg). The second immunization was given at 28 days and the third vaccine was given on day 56. All vaccine doses elicited neutralizing antibodies 14 days after the third dose.
  5. In a 224 patient, Phase II, trial, (ChiCTR2000031809) patients received two immunization of adjuvant alone or 5 mcg of Sinopharm’s COVID-19 vaccine. The second immunization was given at 14 or 21 days. The vaccine elicited neutralizing antibodies 14 days after the third dose at levels greater than adjuvant alone.
  6. The researchers did not compare levels of antibodies to those seen in recovered patients. The researcher claim the levels of neutralizing antibodies in the ChiCTR2000031809 Phase I and II trials were similar to those seen in other COVID-19 vaccine trials. However, different patient populations and different methods to measure antibodies were used, so caution is needed in comparing the levels of neutralizing antibodies.
  7. Sinopharm initiated a 15,000 patient, Phase III trial in the United Arab Emirates on 7/16/2020
  8. Sinopharm announced the efficacy of its COVID-19 vaccine was 79% in a Phase III trial.
Sinovac is developing an inactivated virus vaccine.
  1. The COVID-19 vaccine is given as two immunizations 28 days apart. An emergency schedule is also being tested, where the doses are given 14 days apart.
  2. Sinovac will use Dynavax’s CpG 1018 vaccine adjuvant. CpG 1018 is contained in Dynavax’s HEPLISAV-B (hepatitis-B) vaccine.
  3. A 143 patient Phase I trial was initiated in April (NCT04383574) and Sinovac announced in June that no safety issues were identified.
  4. A 600 patient Phase I/II trial was initiated in April (NCT04352608). In June Sinovac announced the vaccine elicited antibodies in 90% of patients, 14 days after the second immunization, and no safety issues were identified.
  5. In a 743 patient Phase I/II trial (NCT04352608), Sinovac COVID-19 vaccine, CoronaVac, elicited neutralizing antibodies four weeks after two doses of the vaccine given 14 days apart. Based on results from the trial a 3 mcg dose was chosen for Phase III trials. 
  6. Sinovac is evaluating CpG 1018 in a 9,000 patient Phase III trial in Brazil. On 11/9/2020, Brazil halted a 9,000 patient, Phase III trial, examining the safety and efficacy of Sinovac’s CoronaVac to investigate a serious adverse event. The trial was allowed to resume on 11/11/2020 after additional information on the event was provided to Brazilian health authorities. Brazilian researchers originally reported 78% efficacy for the Sinovac Biotech’s COVID-19 vaccine, but lowered the efficacy to 50.4%, when very mild cases were included in the analysis. Interim data from Brazil and Turkey have given different efficacy calculations, so the true protection of the vaccine is unclear
Vaxart is developing the non-replicating adenovirus type-5 (Ad5) viral vector DNA virus, VXA-CoV2-1.
  1. VXA-CoV2-1 is administered as an oral tablet that can be stored at room temperature.
  2. Two doses of the vaccines are given 29-days apart.
  3. Vaxart is evaluating the safety and immunogenicity of a high and low dose of VXA-CoV2-1 in a 48-patient Phase I trial (NCT04563702).
Zydus is developing a DNA vaccine (ZyCoV-D)
  1. Zydus reported the vaccine was well tolerated in a 7-day review of data in a Phase I trial involving an unspecified number of patients.
  2. Zydus initiated a 1,000 patient trial for ZyCoV-D on 8/6/2020