DEVELOPER(S) VACCINE METHOD EVIDENCE STATUS

Moderna and the US government US Lipid nanoparticles containing mRNAs for the SARS-CoV-2 spike protein are injected into the arm. Preliminary results from the early stage trials published in the New England Journal of Medicine in July suggest that the vaccine is safe and elicits higher levels of SARS-CoV-2 antibodies than infection with the virus. A later study published in the same journal reported that vaccinated monkeys quickly cleared the virus. Moderna is developing similar vaccines against Zika and other viruses, but to date, no vaccine of this type has been approved for use. Phase 1, Phase 2, and Phase 3 clinical trials underway across the US

CanSino Biologics and the Academy of Military Medical Sciences China, Canada, Russia, and Saudi Arabia Nonreplicating adenovirus 5 (Ad5) vector carrying the gene for the SARS-CoV-2 spike protein is injected into the arm. Preliminary results from the Phase 2 trial published in The Lancet in July suggest that the vaccine is safe and elicits an immune response, either a T cell response or an antibody response. Adenoviruses are well-established vaccine vectors, and CanSino produced an Ebola vaccine (approved in China in 2017) using the same Ad5 platform. Phase 1 and Phase 2 clinical trials are underway in Wuhan, China. On June 25, following positive Phase 1 data published in The Lancet on May 22, China’s Central Military Commission approved the vaccine’s use by the country’s military for a year. A Phase 1/2 trial has been approved to begin in Canada. A Phase 3 trial has begun in Russia, Reuters reports,and a Phase 3 trial in Saudi Arabia will begin soon.

Inovio Pharmaceuticals US A special device administers spike protein–encoding DNA molecules through the skin. Mice and guinea pigs mounted immune responses against the virus, according to a recent preprint, and the company announced interim results from the Phase 1 trial at the end of June that suggested the vaccine was safe and spurred immune responses in 94 percent of the 36 participants analyzed. Phase 1 clinical trial underway in Pennsylvania, Missouri, and Kentucky with plans to manufacture 1 million doses of its candidate this year

Sinovac Biotech China, Brazil, Bangladesh, and Indonesia Inactivated SARS-CoV-2 In animal studies, the vaccine candidate provides protection against virus strains from different countries. Results from the Phase 2 trial announced in August suggest that the vaccine is safe and elicits an antibody-based immune response. Sinovac had used a similar platform to develop a vaccine against SARS in 2004 that showed promising results in early-stage human trials. A Phase 1/2 clinical trial is underway in China, and Phase 3 trials are underway in Brazil, Bangladesh, Indonesia, and Turkey.

Wuhan Institute of Biological Products and China National Pharmaceutical Group (Sinopharm) China and United Arab Emirates (UAE) Inactivated SARS-CoV-2 In mid-June, Sinopharm announced that nearly all of the more than 1,000 participants who had received two injections of the mid-dose vaccine tested positive for antibodies against SARS-CoV-2. In August, Phase 1/2 trial results published in JAMA indicated that the vaccine is safe and elicited neutralizing antibodies. A Phase 1/2 clinical trial is underway in China. A Phase 3 trial is underway in UAE, and another has been approved to begin in Peru.

Beijing Institute of Biological Products and China National Pharmaceutical Group (Sinopharm) China Inactivated SARS-CoV-2 The two-dose vaccine protects rhesus macaques against SARS-CoV-2, according to a paper published in Cell in early June. In late June, Sinopharm announced results from the early trials that the vaccine was safe and that participants receiving the vaccine had high titers of antibodies. Phase 1/2 clinical trial underway in China

Symvivo Canada Orally administered Bifidobacterium probiotic engineered to carry DNA encoding the SARS-CoV-2 spike protein In addition to this vaccine currently in human testing, two other candidates for COVID-19 are being developed by Symvivo. Phase 1 clinical trial underway in British Columbia and Nova Scotia

Shenzhen Geno-Immune Medical Institute China Immune cells (human dendritic cells and T cells, or artificial antigen presenting cells) are engineered to express a synthetic minigene based on SARS-CoV-2 proteins and injected or infused into the patient. The research institute modifies cells using lentivirus vectors that it has used to develop CAR T cell therapies as well as gene therapies. A Phase 1/2 clinical trial is underway in China for the dendritic cell and T cell–based vaccines, and a Phase 1 trial is underway for a vaccine using artificial antigen presenting cells.

Clover Biopharmaceuticals Australia The vaccine delivers pieces of the SARS-CoV-2 spike protein. The Trimer-Tag platform used is the basis for other viral vaccines in development. Phase 1 clinical trial underway clinical in Australia

Novavax Australia and South Africa Nanoparticles carrying antigens derived from the SARS-CoV-2 spike protein (with Matrix-M adjuvant) In 2012, the company started development on a SARS vaccine that served as the basis for its new SARS-CoV-2 vaccine candidate. Data from the Phase 1/2 trial published in The New England Journal of Medicine in early September shows the vaccine candidate to be safe and elicit immune responses greater than those caused by treatment with COVID-19 convalescent serum. A Phase 1 clinical trial is underway in Australia. In August, the company announced plans for a Phase 2b trial in South Africa.

Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation, Acellena Contract Drug Research and Development Russia Adenovirus vector displaying the SARS-CoV-2 spike protein on its surface Preliminary results from the early stage trial published in September in The Lancet point to the vaccine candidate’s safety and ability to elicit an antibody response. Gamaleya Research Institute Director Alexander Gintsburg announced in May that he and other staff researchers had gotten the vaccine themselves, the AP reports. Phase 1/2 clinical trials are underway in Russia to test liquid and powder forms of the vaccine. In August, Russian President Vladimir Putin said that the country approved the vaccine ahead of a Phase 3 trial.

Immunitor Canada and Mongolia Heat-inactivated plasma from donors with COVID-19 taken as a pill daily for a month The initial safety test will give volunteers the pill for 15 days. Phase 1/2 clinical trial underway in British Columbia and Mongolia

Institute of Medical Biology at Chinese Academy of Medical Sciences, West China Second University Hospital, Yunnan Center for Disease Control and Prevention China Inactivated SARS-CoV-2 Trial organizers announced that the study is moving into its second phase, which will include three dose groups and a placebo group. Phase 1/2 clinical trial underway in China

Imperial College London Self-amplifying RNA molecules are injected into the muscle. The vaccine platform, which is designed to allow researchers to respond quickly to emerging pathogens, received $8.4 million from CEPI last December. “We cannot predict where or when Disease X will strike, but by developing these kinds of innovative vaccine technologies we can be ready for it,” CEPI CEO Richard Hatchett said at the time. A Phase 1 trial is underway in the UK. Researchers in the UK will also test an inhaled form in an early-stage trial.

CureVac Belgium and Germany RNA vaccine; details not disclosed CureVac reported in January that a Phase 1 trial of a comparable vaccine for rabies induced immune responses with just 1 microgram of mRNA, meaning it could be easy to scale up to produce mass quantities. Phase 1 trial underway in Belgium and Germany; company says it could manufacture 10 million doses by that time.

Medicago Virus-like particles that resemble SARS-CoV-2 are produced in a close relative of tobacco. The company has a rotavirus vaccine in clinical trials that is based on virus-like particles, and another for norovirus in preclinical studies. A Phase 1 trial has been approved

Altimmune Undisclosed vaccination delivered intranasally The company is using the same technology to develop a flu vaccine that is in clinical trials. A Phase 2 trial has been approved

AnGes, Japan Agency for Medical Research and Development Japan Engineered circular DNA encoding the SARS-CoV-2 spike protein The vaccine consists of two intramuscular injections. Phase 1/2 trial underway in Japan

Aivita Biomedical US A patient’s own dendritic cells are modified to carry SARS-CoV-2 antigens and then reinfused. Antigen-carrying dendritic cells triggered a response in the same patient’s lymphocytes in vitro. A Phase 1/2 trial has been approved to begin in California.

Genexine South Korea DNA encoding the SARS-CoV-2 spike protein The vaccine was shown to produce neutralizing antibodies in nonhuman primates. Phase 1/2 trial underway in South Korea

Vaxine, Medytox Australia Recombinant SARS-CoV-2 spike protein plus a polysaccharide adjuvant Vaxine developed an experimental swine flu vaccine during the 2009 pandemic. Phase 1 trial approved to begin in Australia

Zydus Cadila India Engineered DNA plasmid encoding a SARS-CoV-2 antigen In a preclinical study, the vaccine neutralized SARS-CoV-2 in a virus neutralization assay. Phase 1/2 trial underway in India

Bharat Biotech India Inactivated SARS-CoV-2 In guinea pigs and mice, the vaccine was safe and elicited an immune response. Phase 1/2 trial underway in India

Janssen US and Belgium Nonreplicating adenovirus 26 (Ad26) vector carrying undisclosed genetic material of SARS-CoV-2 is delivered via intramuscular injection. Janssen published preclinical data in Nature in July demonstrating that the vaccine protected monkeys against SARS-CoV-2 infection. The company is also developing other Ad26-based vaccine candidates, including its Ebola vaccine that was deployed in the Democratic Republic of Congo in November 2019. Early stage clinical trials are underway in the US and Belgium; a Phase 2 trial is scheduled to begin in early September in Spain, Germany, and the Netherlands

Arcturus Therapeutics Singapore Self-replicating mRNA encoding coronavirus proteins The self-replicating mRNA platform is not the basis of any approved medicines, but preclinical results announced in April suggest the vaccine candidate triggers an immune response. Phase 1/2 trial underway in Singapore

University of Queensland Australia Molecular clamp technology presents viral proteins to the immune system. Preclinical work in cell culture showed that the vaccine candidate elicited an immune response that was capable of neutralizing SARS-CoV-2 infection. Phase 1 clinical trial underway in Australia

ReiThera Italy Proprietary replication-defective gorilla adenoviral (GRAd) vector encodes the SARS-CoV-2 spike protein. The vaccine candidate was safe and induced an immune response in animal models, according to the company. Phase 1 trial underway in Italy

Sanofi and GlaxoSmithKline (GSK) US Antigen based on SARS-CoV-2 spike protein (with adjuvant) Sanofi uses the same recombinant DNA technology in a flu vaccine and in a SARS vaccine candidate that never entered clinical trials. Meanwhile, GSK’s adjuvant, AS03, was used in vaccines the company made against the H1N1 and H5N1 pandemic flu viruses. A Phase 1/2 trial underway in the US

State Research Center of Virology and Biotechnology “Vector” Russia Peptide-based vaccine based on a platform developed for an Ebola vaccine candidate Volunteers in the Phase 2 trial are “feeling good,” the Russian consumer safety watchdog Rospotrebnadzor said in a statement, according to Reuters. The Phase 2 trial is complete and results should be published soon, according to Reuters.

Vaxart A pill containing different SARS-CoV-2 antigens After testing five different vaccine candidates in animals, the company chose its lead candidate, which generated immune responses after a single dose, for clinical testing. The company has other oral recombinant vaccine candidates that have shown success in clinical trials. Phase 1 trial approved to begin in the US

NOT YET IN CLINICAL TRIALS



University of Pittsburgh School of Medicine Microneedle patch delivers pieces of the spike protein through the skin. Vaccinated mice produced antibodies specific to SARS-CoV-2 at levels that would likely neutralize the virus, according to a study published in EBioMedicine on April 2. Expected to start clinical testing within a few months of that publication, according to the university

Generex Biotechnology Undisclosed synthetic viral peptides are combined with proprietary Ii-Key immune system activation The company has had success with the Ii-Key technology for other infectious diseases and for cancer in clinical trials. Expected to start clinical testing “within 90 days,” the company announced on February 27

Takis Biotech and Applied DNA Sciences The company is exploring five DNA-based candidates based on the SARS-CoV-2 spike protein. The vaccine candidates contain PCR-produced pieces of linear DNA, as opposed to the more traditional circular plasmids, which could have several advantages including quick production. No vaccines using this approach have yet been tested in humans. Expected to start clinical testing in the fall

Merck A vesicular stomatitis virus (VSV) carries undisclosed viral components The VSV vector is used for Merck’s existing Ebola vaccine. Expected to start clinical testing later this year