Over the past week, we have been bombarded with news of how the Oxford- AstraZeneca vaccine may be linked to blood clots in those who received it. There has been quite a stir over this, and some countries have even temporarily called for a halt in using the vaccine in their populations while investigations are under way.

For us in Malaysia though, we have been hearing much more of the Pfizer-BioNTech mRNA vaccine, since that is the vaccine that was first approved and is being used widely for vaccination in the country.

However, we should be aware that the Oxford-AstraZeneca vaccine is also part of our vaccine package and will be used for mass vaccinations as well. Interestingly this is not an mRNA-based vaccine but actually comprises another group of vaccines called viral vector vaccines.

In this instalment, let’s take a closer look at this group of vaccines which include the Oxford-AstraZeneca vaccine; as well as the CanSino Biologics vaccine from China (which will come to our shores) and the Johnson & Johnson vaccine (being rolled out for use in the US) which are both single-dose vaccines.

What is a viral vector vaccine? In our previous instalment, we explained in length about vaccines and how they work.

The mRNA vaccine contains instructions for human muscle cells, which it is injected into, to produce Covid-19 spike proteins. These spike proteins stick to the surface of the muscle cells into which it was originally injected, become recognised as “alien” by our immune system and subsequently there is an immune response (to destroy it). However, this mRNA is coated in a special coating which protects it from being destroyed as they are on route from the site where the vaccine was injected.

Viral vector vaccines are similar to mRNA vaccines in which they also contain instructions for the muscle cells (of the injected recipient) to produce Covid-19 spike proteins.

The proteins then act to activate the immune system similar to the action of mRNA vaccines. The viral vectors themselves also play an additional role in boosting the body’s immune response better than just vaccinating using parts of the Covid-19 virus.

What is unique is that these instructions are not sent as mRNA which is covered in a special coating (as is the case in mRNA vaccines), but is instead a gene which is “put inside” a different virus – acting as a vector or transmitter. Think about this viral vector as a Grab driver which carries the passenger (the gene for making the spike proteins) into the muscle cells of the person receiving the vaccine.

These virus “carriers” or Grab drivers have the instructions to make spike proteins already attached to them as a specific gene in their own genome. The virus manages to inject itself into the muscle cells of the recipient, where this specific gene goes to work – triggering the cells to produce spike proteins.

The virus carrier is usually a common human virus, which is then modified to become non-dangerous in terms of causing illness in humans; or is a virus that cannot cause disease in humans. For the Covid-19 viral vector vaccines, the virus being used as a vector or carrier is actually from the adenovirus family. One of the reasons why adenoviruses are chosen as viral carriers is because its DNA does not integrate into the genome and thus is not replicated.

Another reason is because they are a group of common viruses which come into contact with humans all the time, causing lung, stomach and eye infections. These infections are usually mild infections which resolve in a few days.

In order to utilise them as viral carriers, these viruses have been further modified to ensure that they themselves are not able to cause further infections or harm in terms of causing disease within the person receiving them.

However, it is this commonality that can prove to be one of the challenges with using adenoviruses as a viral vector. Because most humans often come into contact with adenoviruses, they may have already developed antibodies against it. As such, when you use a viral vector of this type, your body’s immune system may destroy the carrier virus even before it enters the target cell.

While the efficacy of Covid-19 vaccines using human adenoviruses seem to be unaffected, this was the reason behind the choice of the Oxford-AstraZeneca vaccine to use a chimpanzee adenovirus as their viral vector. Since the chimpanzee adenovirus is not common to humans, it is less likely that humans would have immunity to it.

Even though the technology for viral vector vaccines sounds super “space-age”, it’s actually been around since the 1970s. Viral vectors have been used by molecular biologists to deliver genetic material into cells in the context of gene therapy.

In gene therapy, defective genes which cause diseases, including genetic disorders, are looking to be corrected via the delivery of unmutated genes to the patient’s body cells which will then correct the mutations. Viral vectors are also being actively explored for use within the cancer treatment landscape.

Vaccines utilising viral vectors are not unique, as they already exist for another communicable disease – Ebola. These include Merck’s VSV-EBOV (brand name: Ervebo), which uses a vesicular stomatitis virus as a viral vector; and Johnson & Johnson’s Ad26.ZEBOV/MVA-BN-Filo (brand name: Zabdeno) which uses two viral vector components namely a chimpanzee adenovirus and a modified Vaccinia Ankara virus. These have been approved with a few other vaccines still being developed and in the pipeline.

Like the technology behind mRNA, the technology of viral vectors seems to have come to the forefront amid this Covid-19 pandemic. Although it seems to have been done in a hurry, the truth is that the science behind these innovations are decades old; and it is precisely those many years of R&D that have helped these critical breakthroughs during this time of need.

If you would like to get caught up on previous topics covered under this series, they are available as per the links below:

INFOVAX is a community education and awareness series on Covid-19 vaccines brought to you by the Malaysian Medical Association Public Health Society (MMA PHS). Feel free to ask questions and clear your doubts about Covid-19 vaccines by putting them to us at [email protected]. Your questions and answers will be collated and answered in the following sessions.