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

Updated: Sep 24, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: John L Brusch, MD, FACP  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 2.

Table 2. Other Investigational Vaccines (Open Table in a new window)

Vaccine Comments
INO-4800 (Inovio Pharmaceuticals) [61]

DNA-based, 2-dose vaccine. Stable at room temperature for more than 1 y; frozen shipment not needed. Phase 2/3 trial (INNOVATE) ongoing; phase 2 to evaluate 2-dose regimen (1 mg or 2 mg) vs placebo in 400 participants. 

CVnCoV (CureVac) [62] mRNA, 2-dose vaccine. Phase 2b/3 trial (HERALD) began in December 2020 of mRNA 12-mcg dose (2 doses on days 1 and 29) in multiple European and Latin American sites with goal to enroll 35,000. Partnering with Bayer, GlaxoSmithKline, and Novartis for production. 
Recombinant protein adjuvanted vaccine (SP0253; Sanofi and GSK) [63]   Interim phase 2 results (n = 722) showed 95-100% seroconversion after 2 doses with strong neutralizing antibody levels comparable to natural infection. After a single injection, high neutralizing antibody levels were generated in participants with evidence of prior SARS-CoV-2 infection, suggesting strong potential for development as a booster vaccine. Phase 3 trial in the United States, Asia, Africa, and Latin America started in late May 2021 with target enrollment of 35,000. 
S-Trimer with CpG 1018 adjuvant vaccine (Clover and Dynavax) [64]  

Phase 2/3 trial (SPECTRA) of Clover’s protein-based S-Trimer COVID-19 subunit vaccine adjuvanted with Dynavax’s CpG 1018 plus alum. Trial began in March 2021 in Latin America, Asia, Europe, and Africa. Administered as 2 doses, 21 days apart. 

VLA2001 with CpG 1018 adjuvant (Valneva and Dynavax) [65] Inactivated whole virus vaccine. Phase 3 trial (Cov-Compare) in the United Kingdom will compare immunogenicity of VLA2001 with AZD-1222 in ~4,000 adults. 
UB-612 multitope peptide-based vaccine (COVAXX [United Biomedical, Inc]) [66]   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) [66]   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) [67]   Vaccine prototype development utilizing self-assembling protein nanoparticle (1c-SapNP) vaccine platform technology.
PDA0203 (PDS Biotechnology Corp) [68]   Utilizes Versamune T-cell activating platform for vaccine development.
CoVLP (Medicago and GlaxoSmithKline) [67]   Combines Medicago’s recombinant coronavirus virus-like particles (rCoVLP) with GSK’s adjuvant system. Phase 3 trial initiated in March 2021 aims to enroll 30,000 initially, in healthy adults aged 18-65 y, followed by individuals 65 y and older with comorbidities. The trial will take place in 10 countries, initially starting in Canada and the United States.

Covaxin (BBV152; Bharat Biotech and Ocugen) [68]   

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 after a fully enrolled phase 3 trial (n ~25,800). Interim phase 3 results in March 2021 in India reported 81% efficacy. Second interim analysis of phase 3 results in late April 2021 found 78% efficacy against mild-to-moderate infection and 100% efficacy against severe COVID-19. Plans to pursue full U.S. approval (biologics license application [BLA]) instead of an EUA upon recommendation from the FDA.  

Recombinant adenovirus type-5-vectored vaccine (Ad5-vectored vaccine; Sinopharm [China]) [69]  

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. World Health Organization approved vaccine for emergency use in May 2021 to improve distribution to poorer nations via Covax. 

CoronaVac (Ad5-vectored vaccine; Sinovac [China]) [70]   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) [71]

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 first dose (ie, day of dose 2) confirm COVID-19 infection in 0.1% of the vaccine group compared with 1.3% of the placebo group. Vaccine effectiveness, 91.3%. 

hAd5 T-cell (ImmunityBio) [72]  

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) [73] 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) [74]   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.
SARS-CoV-2 spike ferritin nanoparticle (spFN) vaccine with ALFQ adjuvant (Walter Reed Army Institute of Research) [75] Phase 1 study launched April 1, 2021. Preclinical trial in monkeys showed 2-dose vaccine delivered high antibody levels. Development plans include new vaccine version with proteins from other coronaviruses. 
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) [78]  

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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