The world is waiting with bated breath for a functional COVID-19 vaccine. In the past century, vaccines have rescued humankind from many infectious diseases.
What makes designing a potential vaccine for COVID-19 challenging? To answer this question, it is important to understand how a vaccine elicits an appropriate immune response in the body.
Active and passive immunisation
The immune response towards any infection can be passive or active. Passive immunisation is when antibodies are directly transferred from one individual to another. Such passively transferred antibodies accord immediate protection – but it wanes gradually and the individual eventually becomes susceptible to the disease again. It could be natural or artificial.
Placental transfer of antibodies from the mother to the foetus gives natural passive immunity. Convalescent plasma therapy, involving the transfer of plasma containing specific antibodies from recovered individuals to susceptible individuals, provides passive immunity as well.
Vaccines provide active immunisation: they deliberately introduce a foreign substance, called an antigen, into the body to induce the body to mount an immune response. Though the protection is not conferred immediately, the immunity lasts for a considerably longer period once established. Repeated doses of the same antigen could boost immunity further.
How does a vaccine work?
A vaccine works like a virus and initiates an immune response – but without causing major illness.
The immune response is brought on by different types of cells. However, a specialised group of white blood cells, called the B and T lymphocytes, are important to sustain the immune response in the long run.
When an antigen enters the body, cells called dendritic cells get attracted to it, and then carry the antigen to T lymphocytes. The T lymphocytes identify these antigens and bind to them.
Meanwhile, B lymphocytes also pick up the antigens, process them and present them to the T lymphocytes. After this interaction, T lymphocytes release signalling molecules called cytokines, which stimulate the B lymphocytes. In response, the B lymphocytes rapidly turn into plasma and ‘memory’ B cells. One B lymphocyte can produce thousands of such daughter cells in a few days.
The plasma cells are responsible for secreting antibodies that will tackle the antigen and eliminate the infection. And once the infection has been removed from the body, the plasma cells die while ‘memory’ B cells rest in the bone marrow, and keep secreting low levels of antibodies.
When the body is exposed to the same antigen again, the circulating antibodies bind to the antigen. This is what they mean when they say the immune system becomes familiar with the antigen, and the immune response the second time is even more effective. This memory is known as immunological memory, and it forms the basis of vaccination.
Live attenuated and inactivated killed vaccines
Ideally, a vaccine should trigger an adequate immune response without harming the body. There are different types of vaccines to achieve this outcome. Conventional vaccines fall into two broad categories: live attenuated vaccines and inactivated killed vaccines.
Live attenuated vaccines contain whole virus particles. Inducing the virus to replicate under unnatural conditions reduces its virulence. For example, researchers could have injected the virus into an ‘unnatural’ host, causing the virus to eventually lose its adaptation towards the actual host, and transform to a less virulent form. That is, it can no longer cause disease as well as it could before. This process is called attenuation.
The level of attenuation is critical to a vaccine’s success. Over-attenuation could render the vaccine ineffective, while under-attenuation could cause the vaccine itself to produce disease.
The chickenpox, measles, mumps and rubella vaccines are all live vaccines.
Inactivated vaccines contain a part of the virus instead of the whole. During preparation, researchers remove those parts of the virus required for viral replication, making these vaccines safer than the live attenuated type.
On the flip side, inactivated vaccines in general don’t accord long-lasting protection, like live vaccines. Sometimes, a substance called an adjuvant is added to inactivated vaccines to boost the immune response and make them last considerably longer. However, including an adjuvant increases their overall cost.
The COVAXIN vaccine against COVID-19, developed by Hyderabad-based Bharat Biotech, is an inactivated vaccine with alum as adjuvant.
Apart from conventional vaccines, in the last few years, researchers have tried a new generation of vaccines. One of them is a DNA vaccine. The ZyCoV-D vaccine being developed by Zydus Cadila is of this type.
Cells have DNA in their chromosomes – and also outside the chromosomes in a form called plasmids. First, researchers obtain plasmids from a bacterium. Then, they separate some genetic material from the virus and insert it into the plasmid, and inject this plasmid into the body.
The viral genes then integrate themselves into cells in the body and begin to express foreign proteins. This triggers an immune response.
Plasmid DNA can be easily constructed and manipulated by genetic engineering. So it’s not hard to produce DNA vaccines in large volumes – which then means they are quite cost-effective.
However, although experiments with DNA vaccines on animal models have been successful, not one is currently available for human use. One reason is that DNA vaccines have been found to elicit a less pronounced immune response in humans than in animals. Scientists are working on several strategies to overcome this shortcoming.
In this context, if ZyCoV-D successfully completes human clinical trials and is found to be efficacious (and safe), the occasion will undoubtedly break new ground in the history of vaccines.
Niranjana Rajalakshmi is a veterinary microbiologist.