To aid in the fight against the global Covid-19 pandemic, the past year has seen an urgent rush to develop new and effective vaccines at lightning speed.

Tremendous and collaborative efforts have been made by pharma, governments, scientific experts and patient volunteers to find jabs that will protect the population and slow the disruption that Covid-19 has wrought.

A number of promising candidates from some of the world’s biggest pharma companies have emerged and have already been administered to millions globally.

But, for a number of these vaccines it has been an incredibly bumpy road. With the news of both AstraZeneca’s vaccine and now Johnson & Johnson’s candidate being linked to cases of rare blood clots, governments and their populations are now looking hopefully to candidates further down the pipeline without a reputation for serious adverse events.

With dozens all in different stages of development, and new variants of Covid-19 popping over the last year, the race for the safest and most effective vaccines continues with a new crop of candidates.

Clinical Trials Arena tracks the development of the vaccine candidates at the front of that race for approval.

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Candidate name: NVX-CoV2373

Mechanism: Nanoparticle vaccine

Trial phase: Phase III

After assessing safety and immunogenicity in Phase I/II clinical trials where the vaccine produced encouragingly high levels of antibodies, NVX-CoV2373 is currently in two pivotal Phase III studies to evaluate vaccine efficacy, safety and immunogenicity.

NVX-CoV2373 clinical trials have enrolled more than 30,000 volunteers around the globe.

NVX-CoV2373 is a protein-based vaccine engineered from the genetic sequence of SARS-CoV-2, the virus that causes Covid-19.

The candidate was created using US-based Novavax‘s recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is complemented with the company’s patented saponin-based Matrix-M adjuvant to enhance immune response and stimulate high levels of neutralising antibodies.

In March 2021, Novavax reported that its UK trial determined an efficacy rate of 96% against the original coronavirus and 86% against the UK variant. But in South Africa, where volunteers were exposed to variant B.1.351, the efficacy was only 49%.

The company is now developing a new version of the vaccine that is tailored to the South Africa variant. The vaccine has also been brought into a University of Oxford trial to study the potential efficacy of mixing doses of different vaccines, alongside vaccines from Oxford/AstraZeneca, Pfizer/BioNTech and Moderna.

If its own clinical trials succeed, Novavax expects to deliver 100 million doses for use in the United States in 2021.

Zydus Cadila

Candidate name: ZyCoV-D

Mechanism: DNA vaccine (plasmid)

Trial phase: Phase III

ZyCoV-D is India-based Zydus Cadila’s plasmid DNA vaccine candidate for Covid-19 that targets the viral entry membrane protein of the virus.

In early animal studies, the firm reported that as well as generating neutralising antibodies post-vaccination, ZyCoV-D also induced T-cell response.

ZyCoV-D can be stored at 2 to 8°C for the long term and at 25°C for a few months and is administered via Needle Free Injection System (NFIS).

The company has launched an adaptive Phase I/II dose-escalation trial and plans to enrol about 1,000 healthy volunteers. The candidate began Phase II trials in August 2020. The Drugs Controller General of India has granted approval for Zydus Cadila to proceed with Phase III trials which began in January, involving over 30,000 people.


Cuba’s Center for Genetic Engineering and Biotechnology (CIGB)

Candidate name: Abdala (CIGB 66)

Mechanism: Protein subunit vaccine

Trial phase: Phase III

Abdala is one of three vaccine candidates for Covid-19 being developed in-house by Cuba’s Center for Genetic Engineering and Biotechnology (CIGB).

Abdala (CIGB 66) is a protein vaccine that uses yeast as a receptor-binding domain (RBD) protein and alumina as an adjuvant.

The platform used to produce Abdala´s RBD is the same one that the centre used in the past to develop HeberNasVac, a therapeutic vaccine against hepatitis B.

Abdala is designed to be administered three times, at 14-day intervals.

The Cuban government reports that 48,000 doses of the first of three shots of the jab were administered to members of CIGB and healthcare workers in the country, reaching the full population of participants proposed for the trial.

The ABDALA trial moved to Phase III at the end of February 2021.



Candidate name: VIR-7831

Mechanism: Plant-based adjuvant vaccine

Trial phase: Phase III

Medicago uses a plant-based platform to develop its vaccines. This approach uses living plants as bioreactors to produce non-infectious versions of viruses (called virus-like particles, or VLPs).

VLPs mimic the native structure of viruses, helping them to be easily recognised by the immune system.

Medicago developed its seasonal recombinant quadrivalent VLP vaccine candidate, VIR-7831, just 20 days after working with the SARS-CoV-2 genome.

A single dose of VIR-7831 in mice generated a positive antibody response after 10 days. Results from a Phase I trial show the vaccine was tolerable and generated an immune response in all participants after two doses.

Based on these results, Medicago received the agreement of regulatory authorities to launch Phase II/III clinical trials on 12 November 2020.

The company is also testing the candidate with two additional vaccine adjuvants from GSK and Dynavax.

On 17 February, the US FDA granted the candidate Fast Track designation.



Candidate name: CVnCoV

Mechanism: mRNA-based vaccine

Trial phase: Phase IIb/III

CVnCoV is German clinical-stage biopharmaceutical company Curevac’s mRNA-based vaccine candidate, which started development in January 2020. CVnCoV is being developed in collaboration with British pharma giant GlaxoSmithKline (GSK) and Bayer.

The candidate is being supported by the German federal government and its development is strengthened by a partnership with the UK Government and its Vaccines Taskforce, which CureVac entered in February 2021.

The vaccine is an optimised, non-chemically modified mRNA, encoding the prefusion stabilized full-length spike protein of the SARS-CoV-2 virus, and formulated within lipid nanoparticles (LNPs).

Phase I and IIa clinical trials of CVnCoV began in June and September 2020, respectively, in Germany, Belgium, Peru and Panama. Phase I interim data showed that CVnCoV was generally well tolerated across all tested doses and induced strong antibody responses in addition to first indication of T cell activation. CureVac said the quality of immune response was comparable to recovered Covid-19 patients, closely mimicking the immune response after natural Covid-19 infection.

In December 2020, CureVac initiated the HERALD study, a pivotal Phase IIb/III trial taking place in Germany with 36,000 participants, who will receive a 12µg dose of CVnCoV.

A complementary Phase III trial at the University Medical Center Mainz of more than 2,500 healthcare workers is also underway and a Phase III trial in Mexico has also begun.

In February 2021, CureVac initiated a rolling submission with the European Medicines Agency (EMA) for CVnCoV.


Murdoch Children’s Research Institute

Candidate name: Bacillus Calmette-Guerin

Mechanism: Live-attenuated vaccine

Trial phase: Phase II/III

Murdoch Children’s Research Institute in Melbourne, Australia is conducting a Phase III trial of the bacillus Calmette-Guérin (BCG) tuberculosis vaccine to see if it also protects against the coronavirus. The trial, called BRACE, is being run in Australia, Brazil, the Netherlands, Spain and the United Kingdom.

Altogether, the trial will recruit more than 10,000 healthcare staff who will be given either the BCG vaccine (currently given to more than 100 million babies worldwide each year to protect against tuberculosis) or a placebo injection. In the UK, routine BCG vaccination ceased in 2005 because of the low rates of TB in the general population.

The BCG vaccine boosts immunity by ‘training’ the immune system to respond to other subsequent infections with greater intensity.

Previous studies suggest that the BCG vaccine could reduce susceptibility to a range of infections caused by viruses including those similar to the novel coronavirus. This notion is what will be examined by the researchers working on the BRACE trial.

BRACE has received more than $10m from the Bill and Melinda Gates Foundation to allow its global expansion. The Peter Sowerby Foundation has contributed funding to support the UK Exeter trial site.


Inovio Pharmaceuticals

Candidate name: INO-4800

Mechanism: DNA vaccine (plasmid)

Trial phase: Phase II/III

Composed of an optimised DNA plasmid, INO-4800 is delivered via a proprietary smart device to produce “a robust and tolerable immune response”. US drug developer Inovio plans to scale production of the device while awaiting study results.

Inovio said INO-4800 is the only nucleic-acid based vaccine that is stable at room temperature for more than a year, at 37°C for more than a month and has a five-year projected shelf life at normal refrigeration temperature. The candidate does not need to be frozen during transport or storage.

Preclinical data published in Nature Communications showed that mice and guinea pigs who received INO-4800 demonstrated neutralising antibodies as well as humoral and T-cell responses. In guinea pigs, researchers observed protein-binding antibody titers and blocking of angiotensin-converting enzyme 2 (ACE2)/SARS-CoV-2 S proteins.

Inovio has been working with Advaccine to advance the clinical development of INO-4800 in China, where 640 subjects have been dosed with the first vaccination of a 28-day, two-dose regimen in a Phase II clinical trial. The trial has enrolled both adults who are 18-59 years old and older adults over 60 with the primary endpoints of evaluating safety and immunogenicity within the Chinese population.

A similar independently-run Phase II segment of INOVIO’s Phase II/III clinical trial for INO-4800 in the US, called INNOVATE, has started dosing.

In April 2021, Inovio announced results of a study that showed INO-4800 induced a robust T cell response against all spike protein variants tested, which the firm says will be key in providing protection against SARS-CoV-2 variants, in addition to providing similar levels of neutralising activity against both the UK and Brazilian variants as those against the original strain.



Candidate name: hAd5

Mechanism: Adenovirus-based vaccine

Trial phase: Phase I

ImmunityBio is developing a second-generation Covid-19 adenovirus vaccine candidate that targets both spike and nucleocapsid DNA in SARS-CoV-2.

In May 2020, the firm’s vaccine candidate, which is being manufactured by NantKwest, was selected to participate in Operation Warp Speed, a national program to accelerate Covid-19 vaccine development.

ImmunityBio believes the key to creating long-term immunity to the SARS-CoV-2 virus and overcoming the variants that are rapidly developing around the world is to design a vaccine that activates antibodies as well as memory B and T cells to multiple antigens.

The vaccine has the potential to provide multiple routes of administration (subcutaneous, intranasal and oral) to potentially generate mucosal IgA antibody barriers to the virus in the upper respiratory tract where it first enters the body.

The firm’s vaccine demonstrated CD4+ and CD8+ antigen-specific T cell responses in mice and protects nasal and lung airways in non-human primates.

ImmunityBio received authorisation from the US FDA to initiate a Phase I trial of its vaccine candidate last October. Results from the study, and others, will inform the company’s swift movement into its Phase II/III trial design.

Currently, a Phase Ib study of the vaccine is progressing to assess the safety and immunogenicity of subcutaneous, oral and sublingual prime-boost combinations.



Candidate name: UB-612

Mechanism: Multitope peptide-based vaccine

Trial phase: Phase II/III

Vaxxinity (formerly COVAXX), a subsidiary of United Biomedical (UBI), is developing UB-612, a multitope protein/synthetic peptide-based vaccine candidate for Covid-19. UB-612 is designed to activate both T-cell and B-cell immunity in the body and has shown neutralising antibody activity in mice, rats, and guinea pigs.

In Taiwan, a Phase I trial of up to 60 participants is underway, and a Phase II trial of 3,850 participants has been initiated.

Results from the Phase I study, which evaluated the safety, tolerability, and immunogenicity of UB-612, showed that the vaccine was generally well-tolerated and elicited robust vaccine-induced CD4+/CD8+ T cell antibody responses.

Vaxxinity is also partnering with medical company Dasa for a Phase II/III trial in Brazil, and with the University of Nebraska for Phase I/II trials in the United States.


ReiThera, Leukocare & Univercells

Candidate name: GRAd-COV2

Mechanism: Adenovirus-based vaccine

Trial phase: Phase II/III

Biotechnology firms ReiThera (Italy), Leukocare (Germany) and Univercells (Belgium) are partnering to develop GRAd-COV2, an adenovirus-based Covid-19 vaccine.

GRAd-COV2 is based on a novel replication-defective Gorilla Adenovirus and encodes for SARS-COV-2 full-length prefusion stabilised Spike protein.

Pre-clinical results in mice and macaques indicate the vaccine generates an immune and Th1-dominated cellular response.

A Phase I trial of up to 90 healthy participants 18-55 years and 65-85 years old is currently underway in Italy. Preliminary results from this trial demonstrated that the vaccine candidate is safe and well-tolerated.

GRAd-COV2 entered the Phase II/III COVITAR study in March to assess the safety, immunogenicity and efficacy of GRAd-COV2 compared to placebo for the prevention of Covid-19 in adults over the age of 18. ReiThera said the first part of the study will be a Phase II to confirm safety and immunogenicity and select the regimen for Phase III.