Covid-19 Vaccine Update

Researchers worldwide are racing to find a vaccine against the Coronavirus. Experts estimate that a fast tracked vaccine development process could take up to 12-18 months, if the process goes smoothly from conception to market availability. Operation Warp Speed (OWS) is a collaboration of several US federal government departments including Health and Human Services and its sub-agencies, Agriculture, Energy and Veterans Affairs and the private sector. Within OWS, the US National Institutes of Health (NIH) has partnered with more than 18 biopharmaceutical companies to accelerate development of drug and vaccine candidates for COVID-19 (ACTIV).The US government is choosing three vaccine candidates to fund for Phase 3 trials under Operation Warp Speed: Moderna mRNA-1273 in July, The University of Oxford and AstraZeneca’s AZD1222 in August, and Pfizer and BioNTech’s BNT162 in September.

The following is a list of the possible Covid-19 vaccine candidates currently in Phase 1-3 trials.

1. Bacillus Calmette Guerin (BCG) live attenuated vaccine:

Institution: University of Melbourne and Murdoch Children’s Research Institute, Radboud University Medical Center, Faustman Lab at Massachusetts General Hospital. 

Trial Phase: 2/3 

The infectious disease researchers are preparing to roll-out a multicentre randomised controlled clinical trial of the BCG vaccine against COVID-19. The Director-General of the WHO, Tedros Adhanom, has endorsed this trial. He has called for global support and assistance in the fight against COVID-19. There is no evidence that the BCG vaccine protects people against infection with COVID-19 virus. Two clinical trials addressing this question are underway, and WHO will evaluate the evidence when it is available. In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19.

2. AZD1222

Institution: University of Oxford, the Jenner Institute

Trial Phase: 2/3 

The phase I trial in healthy adult volunteers began in April. More than 1,000 immunisations have been completed and follow-up is currently ongoing.

The next study will enrol up to 10,260 adults and children. It will involve a number of partner institutions across the country. Phase II of the study involves expanding the age range of people to include a small number of older adults and children, ages:

•56-69

•Over 70

• 5-12 years

Researchers will be assessing the immune response to find out if there is variation in how well the immune system responds.

The phase III part of the study involves assessing how the vaccine works in a large number of people over the age of 18. This group will assess how well the vaccine works to prevent people from becoming infected and unwell with COVID-19.

Adult participants in both Phase II and Phase III groups will be randomised. They will receive one or two doses of either the ChAdOx1 nCoV-19 vaccine or a licensed vaccine (MenACWY) . That will be used as a ‘control’ for comparison.

ChAdOx1 nCoV-19 is made from a virus (ChAdOx1), which is a weakened version of a common cold virus. That virus causes infections in chimpanzees. That has been genetically changed so that it is impossible for it to replicate in humans.

This trial offered some promise by showing the vaccine was not only safe, but also seemed to build an immune response in the participants. For one, it was found that being injected with the vaccine led to participants building neutralising antibodies. Another potential positive was that it increased the number of T cells. That is a type of white blood cell that protects the body from pathogens and cancer cells and works to actively destroy infected cells.

A single dose of the vaccine elicited an increase in antibodies specifically against the spike protein by the first 28 days. Neutralising antibody responses were detected in 32 of 35 participants studied after a single dose, and in all nine participants assessed after they were administered a second, booster dose.The vaccine showed mild to moderate adverse reactions, including pain, feverish feelings, chills, muscle aches, headaches and malaise. Using prophylactic paracetamol, the effects were reduced.

3. mRNA-1273 (Moderna)

Institute: Kaiser Permanente Washington Health Research Institute, USA

Trial Phase: 2

The vaccine is called mRNA-1273 and made by Moderna. The vaccine is made using a new process that is much faster than older methods of making vaccines. It does not contain any part of the actual coronavirus and cannot cause infection. Instead, it includes a short segment of messenger RNA that is made in a lab. Moderna will enter the Phase-III of human clinical trials. It is currently in large-scale Phase-II trials, which evaluate immunogenicity, dose levels, and adverse effects of the candidate vaccine. In the two phases of the human trials, Moderna Inc’s vaccine has reportedly provoked safe immune responses in all the volunteers. Now, in the third phase, the scientists will administer the vaccine to 30,000 volunteers.

4. BNT162 (Pfizer, BioNTech)

Institution: Multiple study sites in Europe 

Trial Phase: 1/2

The four vaccine candidates are the first candidates from BioNTech’s COVID-19 focused project “Lightspeed”, each representing different mRNA formats and target antigens. The dose escalation portion of the Phase 1/2 trial will include approximately 200 healthy subjects. They will be between the ages of 18 to 55 and will target a dose range of 1 µg to 100 µg aiming to determine the optimal dose for further studies as well as evaluate the safety and immunogenicity of the vaccine. The study will also evaluate the effects of repeated immunization for three of the four vaccine candidates which utilize uRNA. Subjects with a higher risk for a severe COVID-19 infection will be included in the second part of the study. The data also demonstrated an induction of high level of T-cell responses against the virus.The trial showed that volunteers given two doses of the vaccine produced virus-neutralizing antibodies.

5. Inactivated vaccine

Institution: Henan Provincial Center for Disease Control and Prevention, Wuhan, China.

Trial Phase: 1/2

The Phase I/II clinical trials of the world’s first inactivated COVID-19 vaccine, produced antibodies in every participant. Phase I/II clinical trials were randomized,placebo-controlled clinical studies. 

For those aged 18 – 59 received two medium-dose injections through the 14-day and 21-day interval procedures. They had a neutralizing antibody positive conversion rate of 97.6%. For those who received two medium-dose injections at an interval of 28 days, the neutralizing antibody positive conversion rate reached 100%.

6. Covaxin

Institution: Bharat Biotech, India

Phase: 2/3

On the 29th of June, India got the approval for conducting human trials of a potential vaccine. Covaxin, developed by Bharat Biotech is the first COVID-19 vaccine to get approval from DCGI (Drug Controller General of India). This allowed the company to conduct Phase I and II clinical trials. In phase I, the vaccine would be tested on 375 volunteers. India is one of the largest vaccine producers in the world and scientists are hoping to develop a vaccine within months. It will be tested on more than 1,100 people in phase 1 and 2 clinical trials.

Zydus Cadila

Institution: Zydus Research Centre, Ahmedabad, India

Phase: 2/3

Zydus Cadila’s ZyCov-D is a “plasmid DNA” vaccine. DNA vaccines use genetically engineered plasmids which is a type of DNA molecule that are coded with the antigen against which the immune response is to be built. The DNA sequence injected would match that of the virus, helping the body build antibodies against it. The vaccine’s phase I and II trials target 1,048 participants and are to be conducted at one site–Zydus Research Centre in Ahmedabad .ZyCov-D’s first phase of trials is expected to take nearly three months to complete, following which the vaccine will move on to the second phase. CTRI shows that both phases of the trials are expected to take a year to complete.

The rising number of Covid-19 cases across the world has paved the way for fast-tracking of clinical trials of vaccines which are being seen as the only ray of hope in the battle against the virus. Therefore, let us hope that a vaccine is found soon.

For more information on the vaccines and to track how far they have come, click on the link below:

https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker