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Top 3 COVID-19 vaccine candidates and how they work

Rapid development of a safe and effective vaccine is urgently needed to fight the current pandemic; what are the top COVID-19 vaccine candidates?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiates the coronavirus disease discovered in 2019 (COVID-19). SARS-CoV-2 affects respiratory epithelial cells, producing symptoms ranging from fever, dry cough, and shortness of breath (similar to cold and flu), to severe pneumonia in infected individuals.

Vaccines that induce protective and long-lived immune responses are the most useful and cost-effective way of controlling outbreaks. Side effects of vaccinations are usually minimal, consisting of redness and swelling at the injection site and flu-like symptoms.

COVID-19 vaccine clinical trials are currently taking place worldwide to test the safety, efficacy, tolerability, and immunogenicity of a range of candidate vaccines. According to the World Health Organisation, at least 23 COVID-19 vaccine candidates are being tested in humans. A vital structural component of the viral envelope of coronavirus is the surface spike protein; this is considered to be a crucial target for vaccines to protect against COVID-19 infection. At present, the top 3 COVID-19 vaccine candidates are AZD122, mRNA-1273, and BNT162.


The University of Oxford (UK) are working with AstraZeneca to develop a chimpanzee adenovirus vectored vaccine. Non-replicating viral vectors are a form of live attenuated vaccines that adapt current, safe, and successful viral vectors to express coronavirus proteins upon immunisation.

The modified chimp adenovirus vector has been tested in many pre-clinical and clinical trials and has been demonstrated to be safe and effective. 1077 volunteers received the vaccine in the Phase 1-2 trial; all participants had developed neutralising antibodies against COVID-19 when tested after 28 days. However, adverse effects included pain at the injection site, headaches, fever, chills, and muscle ache in more than 60% of participants. The majority of side effects were only moderately severe, indicating that a single dose of AZD1222 is relatively safe and well-tolerated.

Clinical trials for AZD1222 are currently in Phase 3 and appear promising. Healthy adults aged 18 to 55 can participate in the randomized trial and will receive either the investigational vaccine or a meningitis placebo vaccine. The volunteers will be followed for 12 months to analyse the success of the vaccine in preventing COVID-19 using blood samples. The study will be completed in August 2021.


The first vaccine in clinical trials in the United States was the mRNA-1273 vaccine. This RNA vaccine is being developed by the National Institute of Allergy and Infectious Disease (NIAID) in collaboration with the biotechnology company Moderna.

mRNA-1273 consists of a lipid nanoparticle dispersion containing messenger RNA (mRNA). This non-replicating RNA vaccine targets the spike protein by inducing S protein production in host cells, causing an antibody response to occur. mRNA vaccines have higher potency, shorter generation cycles, and increased safety due to a lack of viral genome in comparison to conventional vaccines.

The clinical trial was initially conducted in 45 healthy adult volunteers aged 18 to 55 with two vaccinations, 28 days apart. Different doses of the vaccine were tested (25, 100, and 250µg). mRNA-1273 was demonstrated to produce neutralising antibodies and T-cell responses against COVID-19. mRNA-1273 was also generally well-tolerated, although more than 50% of recipients reported fatigue, headaches, muscle pain, chills, and pain at the injection site. Higher doses were associated with increased antibody responses and more adverse events. The 100µg dose was found to produce high neutralisation and T cell responses, as well as ensure suitable tolerability in participants.

mRNA-1273 has now progressed to Phase 3 COVID-19 vaccine clinical trials. According to NIAID Director, Dr Anthony Fauci, “Results from early-stage clinical testing indicate the investigational mRNA-1273 vaccine is safe and immunogenic, supporting the initiation of a Phase 3 clinical trial. This scientifically rigorous, randomized, placebo-controlled trial is designed to determine if the vaccine can prevent COVID-19 and for how long such protection may last.”


Nucleic acid vaccines can be rapidly produced and contain no live virus. BioNTech and Pfizer have sponsored key COVID-19 vaccine candidates, which are now in Phase 2-3 trials in the United States and Germany.

The BNT162 vaccines include at least four experimental vaccines with different mRNA formats and target antigens. BNT162b1 and BNT162b2 are both nucleoside-modified RNAs in lipid nanoparticles. BNT162b1 encodes an optimized SARS-CoV-2 receptor-binding domain (RBD) antigen, while BNT162b2 encodes an optimized SARS-CoV-2 spike protein antigen.

A clinical trial of the BNT162b1 vaccine applied the mRNA-based vaccine to 45 healthy participants aged 19 to 54. BNT162b1 treatment was found to induce immunity and prevent COVID-19 infection. Adverse effects were dose-dependent and included pain at the injection site, fatigue, and headaches.

BNT162b2 has progressed to a Phase 2-3 trial, which includes 30,000 participants between the ages of 18 to 85 across 120 global sites. At the beginning of August 2020, Pfizer Canada and BioNTech SE announced their plans to distribute BNT162 vaccine candidates in Canada to prevent COVID-19 infection following clinical success and Health Canada approval.

More medical research is required to fully understand the effectiveness of these vaccines in the prevention of COVID-19. Professor Adrian Hill, Director of Oxford’s Jenner Institute, stated, “We feel that there’s urgency and pressure really every day. People are working day and night and we’re not going to stop until we get an answer.”

Written by Albina Babu, MSc


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Image by Ulrike Leone from Pixabay 



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