High Three COVID-19 vaccine candidates and the way they work – Medical Information Bulletin

The rapid development of a safe and effective vaccine is urgently needed to combat the current pandemic. What are the best COVID-19 vaccine candidates?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers the coronavirus disease (COVID-19) discovered in 2019. SARS-CoV-2 affects epithelial cells of the respiratory tract and causes symptoms such as fever, dry cough and shortness of breath (similar to the common cold and flu) to severe pneumonia in infected people.

Vaccines that create protective and long-lasting immune responses are the most useful and inexpensive way to fight outbreaks. The side effects of vaccinations are usually minimal and consist of redness and swelling at the injection site and flu-like symptoms.

Clinical trials of COVID-19 vaccines are currently underway around the world to test the safety, efficacy, tolerability, and immunogenicity of a number of vaccine candidates. At least 23 COVID-19 vaccine candidates will be tested in humans, according to the World Health Organization. An important structural component of the coronavirus viral envelope is the surface spike protein. This is seen as a critical target for vaccines to protect against COVID-19 infections. Currently, the top three COVID-19 vaccine candidates are AZD122, mRNA-1273, and BNT162.

AZD1222

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

The modified chimpanzee adenovirus vector has been tested in many preclinical and clinical studies and has been shown to be safe and effective. 1077 volunteers received the vaccine in the phase 1-2 study; All participants had developed neutralizing antibodies to COVID-19 when tested after 28 days. However, side effects included injection site pain, headache, fever, chills, and muscle pain in more than 60% of participants. Most of the 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 between the ages of 18 and 55 can participate in the randomized trial and receive either the investigational vaccine or a meningitis placebo vaccine. The volunteers will be followed for 12 months to analyze the success of the vaccine in preventing COVID-19 from blood samples. The study will be completed in August 2021.

mRNA-1273

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

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

The clinical study was initially carried out on 45 healthy adult volunteers aged 18 to 55 years with two vaccinations 28 days apart. Different doses of the vaccine were tested (25, 100 and 250 µg). MRNA-1273 has been shown to produce neutralizing antibodies and T cell responses against COVID-19. mRNA-1273 was also generally well tolerated, although more than 50% of recipients reported fatigue, headache, muscle aches, chills, and pain at the injection site. Higher doses were associated with increased antibody responses and more adverse events. It was found that the 100. g-dose causes a high neutralization and T-cell reaction and ensures adequate tolerability among the participants.

mRNA-1273 has now moved to phase 3 clinical trials with COVID-19 vaccines. According to NIAID director Dr. Anthony Fauci “The results of early-stage clinical tests show that the mRNA 1273 vaccine is safe and immunogenic in the study, which supports the initiation of a phase 3 clinical trial. This scientifically rigorous, randomized, placebo-controlled study aims to determine whether the vaccine can prevent COVID-19 and how long that protection can last. "

BNT162 mRNA

Nucleic acid vaccines are quick to manufacture and do not contain a live virus. BioNTech and Pfizer have sponsored key COVID-19 vaccine candidates that are currently in phase 2-3 trials in the US 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.

In a clinical study with the BNT162b1 vaccine, the mRNA-based vaccine was used in 45 healthy volunteers aged 19 to 54 years. Treatment with BNT162b1 was found to induce immunity and prevent COVID-19 infection. The side effects were dose related and included injection site pain, fatigue, and headache.

BNT162b2 conducted a Phase 2-3 study involving 30,000 participants between the ages of 18 and 85 in 120 locations worldwide. In early August 2020, Pfizer Canada and BioNTech SE announced their plans to distribute BNT162 vaccine candidates in Canada to prevent COVID-19 infection after clinical success and approval from Health Canada.

More medical research is needed to fully understand the effectiveness of these vaccines in preventing COVID-19. Professor Adrian Hill, director of the Jenner Institute in Oxford, said, "We believe that there really is urgency and pressure every day. People work day and night and we won't stop until we get an answer."

Written by Albina Babu, MSc

References:

Folegatti, P.M., et al. (2020). Safety and Immunogenicity of the ChAdOx1 nCoV-19 Vaccine Against SARS-CoV-2: A Preliminary Report of a Phase 1/2 Randomized Controlled Single-Blind Study. The lancet. Retrieved from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/fulltext

Jackson, L.A., et al. (2020). An mRNA vaccine against SARS-CoV-2 – preliminary report. New England Journal of Medicine. Retrieved from: https://www.nejm.org/doi/10.1056/NEJMoa2022483

COVID-19 vaccine candidates are showing promising early results, but the finish line is still well ahead (2020). Abc news. Retrieved from: https://abcnews.go.com/Health/covid-19-vaccine-candidates-show-promising-early-results/story?id=71878984

The clinical phase 3 study of the investigational vaccine against COVID-19 will begin (2020). NIH. Retrieved from: https://www.nih.gov/news-events/news-releases/phase-3-clinical-trial-investigational-vaccine-covid-19-begins

Poland, G.A., Ovsyannikova, I.G. and Crooke, S.N. (2020). Development of SARS-CoV-2 vaccines: current status. In Mayo Clinic Proceedings. Elsevier.

A phase III study investigating a vaccine against COVID-19 (2020). ISRCTN. Retrieved from: http://www.isrctn.com/ISRCTN89951424

Study describing the safety, tolerability, immunogenicity, and effectiveness of RNA vaccine candidates against COVID-19 in healthy adults (2020). NIH. Retrieved from: https://www.clinicaltrials.gov/ct2/show/NCT04368728

Illi, B. (2020) The Long and Winding Road to Covid-19 Treatments and Vaccines, Part 2: From Treating Cardiovascular Diseases to Developing Vaccines. Institute for Molecular Biology and Pathology.

Zhang, J., Xie, B. and Hashimoto, K. (2020). Current status of potential therapeutic candidates for the COVID-19 crisis. Brain, Behavior, and Immunity, 87, pp. 59-73.

BNT162 SARS-CoV-2 vaccine (2020). Precision vaccinations. Retrieved from: https://www.precisionvaccinations.com/vaccines/bnt162-sars-cov-2-vaccine

Image by Ulrike Leone from Pixabay