The efficacy of the Covid-19 vaccines is generally great, with some vaccines cited beyond 95 per cent
BY PROF DR JAMALLUDIN AB RAHMAN (Department of Community Medicine Kulliyyah (Faculty) of Medicine, International Islamic University Malaysia),
ASSOC PROF DR MOHAMAD HANIKI NIK MOHAMED (Department of Pharmacy Practice Kulliyyah (Faculty) of Pharmacy, International Islamic University Malaysia), and
ASSOC PROF DR MISZAIRI SITIRIS (Department of Fiqh & Usul al-Fiqh Kulliyyah (Faculty) of Islamic Revealed Knowledge and Human Sciences, International Islamic University Malaysia).
COVID-19 vaccines are being developed at a historical amount and pace. Over 300 vaccine candidates were recorded, but most are still in the pre-clinical phase, with over 80 candidates are in the clinical trial phase and 12 are currently in use. Are the vaccines effective?
Efficacy is how good the vaccines are during the trial, and effectiveness is their performance in the community. The efficacy of the vaccines is generally great, with some vaccines cited beyond 95 per cent prevention from the infection and there are many reports on how the vaccines were able to reduce the severity of illness in the Phase 3 trials.
However, there are still not enough published population-based scientific papers to prove how effective the vaccines are. Looking at data from the United Arab Emirates (UAE) and the United States (US) (Figure 1.b-d) and assuming how the tests were done and how the cases were reported to remain the same, we can see that the number of cases started to go down around Jan 5, 2021 for both countries. At that time, the vaccination coverage in the population was lower than 10 per cent.
While the vaccination coverage was steadily increasing over time, reaching more than 60 per cent and 25 per cent by March 2021 in UAE and the US respectively, the reported Covid-19 cases were going lower from 700 to 200 per million people in the US and from 350 to 300 per million in the UAE.
This reduction of reported cases may not be directly due to the vaccination programmes because the vaccines require two doses to complete, and it may take from a few days to weeks before an antibody is developed inside the body. But at least the trend is not going up.
Vaccines are used for immunisation purposes to reduce risks of getting specific diseases. In the case of Covid-19, the antigen is typically the characteristic ‘spike protein’ found on the surface of the coronavirus or SARS-CoV-2,which is normally used to help it invade human cells.
Each vaccine candidate must undergo series of stepwise screening and evaluation to determine which antigen should be used to invoke the desired immune response.
This is known as the preclinical phase and is conducted in the laboratory involving the use of model animals such as rats. Once the vaccine that triggers an immune response is identified, it is then tested in humans which is also known as clinical trial (Phase 1 to 3), followed by continuous monitoring or pharmacovigilance in Phase 4.
The vaccine is given to a small number of volunteers (e.g., 20 to 80) to assess its safety, confirm it generates an immune response, and determine the right dosage. Generally, in this phase vaccines are tested in young, healthy adult volunteers.
Candidate vaccines that pass Phase 1 are then given to several hundred volunteers (e.g. 100 to 300) to further assess its safety and ability to generate an immune response. Participants in this phase have similar characteristics (such as age, sex) as the people for whom the vaccine is intended. There are usually multiple trials in this phase to evaluate various age groups and different formulations of the vaccine. A group that did not get the vaccine is usually included in this phase as a comparator group.
The vaccine is given to thousands of volunteers (eg 1000 to 3000) and compared to a similar group of people who did not get the vaccine, but received a comparator product, if available, or placebo (i.e. without any antigen) to determine if the vaccine is effective against the disease it is designed to protect against and to study its safety in a much larger group of people. Most of the time Phase 3 trials are conducted across multiple countries and multiple sites within a country to assure the findings of the vaccine performance apply to many different populations.
Note that during the Phase 2 and Phase 3 trials, the volunteers and the scientists or researchers conducting the study are shielded from knowing which volunteers had received the vaccine being tested or the comparator product or placebo.
When the results of all these clinical trials are available, a series of steps is required, including reviews of efficacy and safety for regulatory approvals.
Further monitoring takes place in an ongoing way after the vaccine is introduced. There are systems to monitor the safety and effectiveness of all vaccines. This enables all stakeholders to keep track of the vaccine impact and safety as they are used in a large number of people, over a longer time frame. This data is used to adjust the policies for vaccine use to optimise their impact and they also allow the vaccine to be safely tracked throughout its use.
This is known as pharmacovigilance. In Malaysia, the Malaysian Adverse Drug Reaction Advisory Committee (MADRAC) under the Drug Control Authority (DCA) is responsible to perform pharmacovigilance activities for all medicinal products registered, including Covid-19 vaccines.
Types of vaccines
There are four types of vaccines: nucleic acid (RNA and DNA), viral vector, protein subunit and whole virus.
Nucleic acid vaccines use mRNA (messenger RNA) or DNA that direct production of other proteins which will then trigger an immune response. The technology for developing mRNA vaccine is well established, contributing to the relatively speedy production and testing of Covid-19 mRNA vaccines, including by Moderna and Pfizer/BioNTech (Comirnaty®). The mRNA vaccines have strands of genetic material inside a special coating which protects the mRNA from degradation by enzymes in the body so that it can then enter the cells to exert its action.
Viral vector-based vaccines use the body’s own cells to produce antigens since the vaccines do not contain antigens.
Instead, the vaccines use a modified virus (the vector) to deliver the genetic code for the antigen into human cells. An immune response is then triggered by infecting cells and instructs them to make large amounts of antigen.
The virus acting as the vector is itself harmless, and by getting the cells only to produce antigens the body can mount an immune response safely, without developing the disease. Examples of viral vector vaccines include those by Oxford/ AstraZeneca, Gamaleya (Sputnik V) and Janssen/Johnson & Johnson.
Whole virus vaccines use a weakened (attenuated) or deactivated form of the pathogen (e.g. coronavirus) that causes a disease (e.g. Covid-19) to trigger protective immunity to it. Live attenuated vaccines use a weakened form of the virus, which can still grow and replicate, but does not cause illness.
Inactivated vaccines contain viruses whose genetic material has been destroyed by heat, chemicals, or radiation so they cannot infect cells and replicate but can still trigger an immune response. Both live attenuated and inactivated vaccines contain the whole or part of the disease- causing pathogen, but the type of immunity they trigger is slightly different.
Examples of Covid-19 vaccines of this type include CoronaVac® by SinoVac.
Protein subunit vaccines (sometimes called acellular vaccines) contain purified pieces of the virus which have been specially selected for their ability to stimulate immune cells. Since these fragments are incapable of causing any actual disease, subunit vaccines are considered very safe.
There are several types of this vaccine, i.e., protein subunit vaccines which contain specific isolated proteins from viral or bacterial pathogens; polysaccharide vaccines which contain chains of sugar molecules (polysaccharides) found in the cell walls of some bacteria; and conjugate subunit vaccines which bind a polysaccharide chain to a carrier protein to try and boost the immune response.
Currently only protein subunit vaccines are being developed against coronavirus that causes Covid-19. — The Health