Which coronavirus disease 2019 (COVID-19) vaccines are still in earlier phases of development?

Updated: Feb 28, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; more...
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Additional vaccine candidates are in various stages of development and clinical testing. Examples of these vaccines are provided in Table 3.

Table 3. Other Investigational Vaccines (Open Table in a new window)

Vaccine Comments
INO-4800 (Inovio Pharmaceuticals) [30]

Stable at room temperature for more than 1 y; frozen shipment not needed; interim results from phase 1 human trial (n = 40): favorable safety and immunogenicity; expanded to include older participants. [31] Phase 2/3 trial (INNOVATE) ongoing; phase 2 to evaluate 2-dose regimen (1 mg or 2 mg) vs placebo in 400 participants.


Grant from the Bill and Melinda Gates Foundation to accelerate testing and scale up a smart device (Cellectra 3PSP) for large-scale intradermal vaccine delivery. It has also received funds from the US Department of Defense.

CVnCoV (CureVac) [32] Phase 2b/3 trial (HERALD) was initiated in December 2020 of mRNA 12-mcg dose (2 doses on days 1 and 29) in multiple European and Latin American sites with goal of 35,000 participants enrolled. Partnering with Bayer and GlaxoSmithKline for production. 
Next generation COVID-19 vaccines (GlaxoSmithKline [GSK] and CureVac) [33]   Codevelopment agreement for mRNA vaccine candidates, including multivalent and monovalent approaches to enable response to new viral variants. Will build on CureVac’s CVnCoV. 
Recombinant protein adjuvanted vaccine (Sanofi and GSK) [34]   Randomized, double-blind, multi-center dose finding study conducted in adults aged 18 years of age and older to evaluate the safety, reactogenicity, and immunogenicity of 2 injections given 21 days apart. The trial will include equal numbers of adults aged 18-59 years and those aged 60 years and older. Study initiated Q1 2021 plans to refine antigen formulation to achieve optimal immune response in older adults. Previous phase 1/2 study showed lower immune response in adults, likely owing to insufficient concentration of antigen.
CpG 1018 adjuvant vaccine (Clover and Dynavax) [35]  

Phase 2/3 trial of Clover’s protein-based S-Trimer COVID-19 subunit vaccine adjuvanted with Dynavax’s CpG 1018 plus alum planned for early 2021. 

UB-612 multitope peptide-based vaccine (COVAXX [United Biomedical, Inc]) [36]   Comprised of SARS-CoV-2 amino acid sequences of the receptor binding domain (RBD). Further formulated with designer Th and CTL epitope peptides derived from the S2 subunit, membrane, and nucleoprotein regions of SARS-CoV-2 structural proteins for induction of memory recall, T-cell activation, and effector functions against SARS-CoV-2. Starting phase 2 trial in Taiwan and phase 2/3 trial in Brazil in Q1 2021. Covaxx is merging with its sister company (United Neuroscience) to form a new company call Vaxinity to include both companies’ vaccine platforms. 
HaloVax (Hoth Therapeutics; Voltron Therapeutics) [37]   Collaboration with the Vaccine and Immunotherapy Center at Massachusetts General Hospital. Use of VaxCelerate self-assembling vaccine platform offers one fixed immune adjuvant and one variable immune targeting to allow rapid development.
Nanoparticle SARS-CoV-2 vaccine (Ufovax) [38]   Vaccine prototype development utilizing self-assembling protein nanoparticle (1c-SapNP) vaccine platform technology.
PDA0203 (PDS Biotechnology Corp) [39]   Utilizes Versamune T-cell activating platform for vaccine development.
CoVLP recombinant coronavirus Virus-Like Particles (Medicago and GlaxoSmithKline) [40]   Combines Medicago’s recombinant coronavirus virus-like particles (rCoVLP) with GSK’s adjuvant system. Phase 2/3 trial started November 2020.

Covaxin (Bharat Biotech and Ocugen) [41]   

Whole-virion inactivated COVID-19 vaccine candidate. Developed and manufactured in Bharat Biotech’s bio-safety level 3 biocontainment facility. Co-development with Ocugen announced for the US market. Received EUA in India in January 2021 following a fully enrolled phase 3 trial (n ~25,800).

Recombinant adenovirus type-5-vectored vaccine (Ad5-vectored vaccine; Sinopharm [China]) [42]  

Approved in China and Saudi Arabia; preliminary data: 86% efficacy; phase 2 trial: seroconversion of neutralizing antibodies seen in 59% and 47% of those in 2-dose groups; seroconversion of binding antibody seen in 96-97% of participants; Positive specific T-cell responses seen in 88-90% of participants. 

CoronaVac (Ad5-vectored vaccine; Sinovac [China]) [43]   Limited use in China. Interim phase 3 efficacy reports vary widely from several trials. A trial in Brazil reports efficacy of 50-90%. However, a Turkish trial reports 91.25% efficacy (n = 7,371; data analysis based on 1322 participants – 752 vaccine and 570 placebo).
rAd26 (frozen) and rAd5 vector-based (lyophilized) formulations (Sputnik V; Moscow Gamaleya Institute) [44]

Approved in Russia. Each vaccine vector carries gene for full-length SARS-CoV-2 glycoprotein S. The phase 3 trial administered 2 doses 21 days apart (rAd26 then rAd5) assigned in a 3:1 ratio of vaccine (n = 16,501) or placebo (n = 5,476). Interim analysis of results 21-days after the first dose (ie, day of dose 2) showed confirm COVID-19 infection in 0.1% of the vaccine group compared with 1.3% of the placebo group translating to 91.3% efficacy. 

hAd5 T-cell (ImmunityBio) [45]  

Phase I trial of second-generation human adenovirus serotype 5 vaccine initiated in October 2020. The vaccine is designed to target inner nucleocapsid (N) and outer spike (S) protein, which have been engineered to activate T cells and antibodies against SARS-CoV-2, respectively. These dual constructs offer the possibility for the vaccine candidate to provide durable, long-term cell-mediated immunity with potent antibody stimulation to patients against both the S and N proteins.

Phase 1 trial expanded to include the initial SC prime vaccine with a room-temperature oral or sublingual booster to induce comprehensive immune protection and generate both systemic and mucosal antibodies. 

MRT5500 (Sanofi and Translate Bio) [46] mRNA-based vaccine candidate. Preclinical evaluation demonstrated favorable ability to elicit neutralizing antibodies using a 2-dose schedule administered 3 weeks apart in Fall 2020. Despite this, Sanofi announced the vaccine will not be ready to start clinical trials until second half of 2021 and it could be of use at a later stage against variants.
AG0302-COVID19 (AnGes and Brickell Biotech) [47]   Adjuvanted DNA vaccine in phase 1/2 study in Japan. Data readouts expected in Q1 2021. Intent to follow with phase 3 trials in United States and South America.
EPV-CoV-19 (EpiVax)  Subunit, T-cell epitope-directed vaccine. Preclinical validation studies completed. Clinical trial anticipated in early 2021. 

Discontinued vaccine development

Vaccine candidates V590 and V591 (Merck) [48]  

V590 and V591 (subunit vaccines): Phase 1 studies showed immune responses were inferior to natural infection and those reported for other SARS-CoV-2 vaccines. 


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