Is the upcoming COVID-19 vaccine a magic stick for the pandemic?

Is the upcoming vaccine our way out from the current dilemma and the source of immunity against the virus which has already affected about 93 million people with about 2 million deceased worldwide up to mid-January 2021? Let us try to understand more about the facts: under normal circumstances, vaccine development is a long and complex process, taking at least 10 years before commercialization. With the development of DNA engineering and the amount of money put into research and development since early 2020 by different countries or regions, the duration has been substantially decreased.

The COVID-19 Prevention Network, or COVPN, had a systemic Clinical Study after the interventions that have shown promise in the laboratory and then in animal model. It subsequently moved on to research studies with human testing. The COVPN will conduct studies to find safe and effective vaccines and monoclonal antibodies for the severe acute respiratory syndrome coronavirus type 2, SARS-CoV-2, which is the virus that causes coronavirus disease 2019, COVID-19.

Initially, in phase 1, the vaccine is given to a small number of generally healthy people to assess the safety of the jabs with increasing doses and to gain early information about how well the vaccine works to induce an immune response in the human body. In the absence of safety concerns from phase 1 of the study, phase 2 includes more people, where various dosages are tested in randomized-control studies on hundreds of people with typically varying health statuses from different demographic groups. The study provides additional safety information on common short-term side effects and risks, examines the relationship between the doses administered and the immune response, and may provide initial information regarding the effectiveness of the vaccine. In phase 3, the vaccine is generally administered to thousands of people in randomized, controlled studies involving broad demographic groups (i.e. the population intended for receiving the vaccine) and generates critical information on effectiveness and additional important safety data. This phase provides additional information about the immune response in people who received the vaccine compared to those in the control group, i.e. the people who were given a placebo.

As at 20th December 2020, there are over 200 candidate vaccines for the coronavirus, of which 52 have started clinical trials, according to the World Health Organization (WHO). Vaccine development is mainly carried out by cultivating viruses, but new techniques using genetics to shorten development time have also emerged. 

Vaccines made using genetic materials like RNA can be developed in a shorter period than those made through conventional processes. Researchers do not need to spend time cultivating the virus. However, there is no existing candidate suitable for human use, and obstacles like verifying safety and efficacy are formidable. RNA and DNA vaccines use RNA or DNA fragments, which are the basis for the virus’ proteins (virus proteins/viral proteins?), but there are also viral vector vaccines, which use another virus that incorporates the genetic information of the coronavirus. Artificial genetic material called “messenger RNA (mRNA)” is made based on genetic data from the coronavirus. Those materials are then incorporated into nanoparticles like lipids to make a vaccine. When administered to the body, the virus’ protein (virus proteins/viral proteins?) (antigen) is produced, and the immune system produces antibodies in response.

Conventional vaccines are made by cultivating the virus in cells and eliminating its ability to infect, or removing part of the virus. Inoculation on humans with it then triggers immune response and prevents future infection. Such progress is reliable because these vaccines use existing methods of development. There are inactivated vaccines, which use a virus that has lost the ability to infect, as well as subunits that use part of the virus and virus-like particles, which use particles with a structure similar to the virus’s own. This type of vaccine uses a virus that has lost its pathogenicity through chemical treatment. Multiple immunizations are often required to obtain immunity because the immunity produced by the body is weak.

Paul Offit, MD, a member of the FDA advisory panel that recommended the vaccine’s use, said rigorous clinical trial of the shot identified no safety concerns, despite the production speed-up. “These vaccines were subject to large phase III clinical trials,” says Offit, a vaccine expert at Children’s Hospital of Philadelphia. “Regarding safety, there was an insistence by the FDA that at least tens of thousands of people be observed for 2 months after the final dose to make sure that there were no……uncommon side effect.” Before EUA approval by FDA.

Under section 564 of the Federal Food, Drug, and Cosmetic Act, the FDA Commissioner approved on 11th December, 2020 the use of the first COVID-19 vaccine by Pfizer-BioNTech (95% effective), and a second one by  Moderna (94.1% effective) on 18th December, 2020 under the conditions of “Emergency use authorization”.

In the U.S., post-authorization vaccine safety monitoring is a federal government responsibility shared primarily by FDA and the U.S. Centers for Disease Control and Prevention (CDC), along with other agencies involved in healthcare delivery. Post-authorization safety monitoring during the COVID-19 pandemic vaccination program will aim to continuously monitor the safety of COVID-19 vaccines to rapidly detect safety problems if they exist. There will be multiple, complementary systems in place with validated analytic methods that can rapidly detect signals for possible vaccine safety problems. The U.S. government has a well-established post-authorization/post-approval vaccine safety monitoring infrastructure that will be scaled up to meet the needs of a large-scale COVID-19 vaccination program. The U.S. government – in partnership with health systems, academic centers, and private sector partners – will use multiple existing vaccine safety monitoring systems to monitor COVIS-19 vaccines in the post authorization/approval period. Some of these systems are the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (VSD), the Biologics Effectiveness and Safety (BEST) Initiative, and Medicare claims data.

The FDA says common side effects, in the clinical trial involving some 44,000 people conducted by Pfizer and 30,000 people by Moderna , included pain where they got the shot, fatigue, headache, chills, fever and joint and muscle pain. But these are all described as temporary, or transient. The symptoms were generally mild or moderate, and happened more frequently after the second dose as the vaccine gets the body ready to fight the disease, while some of the things the body does to fight the virus makes one feel a little under the weather. That is because the vaccine is like a training program for the immune system. A lot of what the body does, such as the immune system cells that are stimulated, or the antibody production that is underway, can make the body feels  not so good for a day or 2.

There were already cases of possible extreme allergic reaction within minutes of injection both in the U.K. and U.S. FDA already required Pfizer to increase its monitoring for anaphylaxis and submit data on it once the vaccine comes into future use. CDC said people with allergies could be safely vaccinated, with close monitoring for 30 minutes after receiving the shot. The FDA panel decided against recommending avoidance of the Pfizer shot among people with a history of allergic reaction to vaccines, a position later echoed by the CDC.

As per news reports in mid January 2021, 23 seniors died of symptoms of side effect after vaccine inoculation in Norway and Germany, among which a high proportion of them were over 80 years old.

The above is a description of facts up to mid-January 2021. Let us have a look at what we are facing at home.

The Hong Kong Government has announced that around February, 2021 onward, mass inoculation will be available in Hong Kong and the first vaccine to arrive will be the one produced by Pfizer and BioNTech which is a mRNA product, as well as the “CoronaVac” developed by Sinovac Biotech, which is an inactivated vaccine. 

According to the information from Brazil, the effectiveness of “CoronaVac'' is 78% when all mild, moderate and severe cases are taken into account. As far as the very mild cases are concerned, however, the figure is 50.38% among the 13,000 volunteers. Moreover, it has been approved for emergency use among high risk groups in China only since July 2020. 

Now the Government has announced that they will take up liability of the side effect after vaccine inoculation in principle, but no particular detail was released on the physical arrangement. There are still a lot of uncertainties for people aged below 16 and above 85, and pregnant and breastfeeding mothers who were not tested during the Phase III clinical trial. How effective are the vaccines on the new UK, South Africa and Brazil strains? How long will the effect of each vaccine last?

How will the Government monitor and follow up the vaccines inoculation among citizens? Can those vaccines stop contagious, asymptomatic infection? How long will the vaccines be effective?

In view of all the above, as I am not a frontline medical worker, nor do I belong to an identified high risk group, I will wear a mask, maintain personal hygiene and social distance, and wait until I know more about the vaccines.

Eric Chan 
Mid-January, 2021