When Russia registered the world’s first COVID-19 vaccine “Sputnik V” on August 11, it was indeed promising news for many who were desperate for prevention against the novel virus. However, the excitement did not last long when experts around the world began questioning the claims made for the vaccine. Especially, the fact that Sputnik V has not entered phase III clinical trial has raised much concern about its safety and efficacy. Further, the lack of proper data pertaining to phase I and II trials have deepened the ongoing skepticism. Before understanding how vaccine trials play a crucial role in determining its efficacy, it would be beneficial to know how the vaccine works.
How does Sputnik V work?
Traditional vaccines belong to the live or inactivated type. Live vaccines contain whole virus particles, the virulence of which is reduced under laboratory conditions. On the other hand, inactivated vaccines contain only a part of the virus that is essential for its replication.
Over the years, scientists have endeavored to produce various next-generation vaccines, thanks to the advances in biotechnology. Next-generation vaccines are highly adaptable and play an important role in speeding up vaccine development. Sputnik V is one of them that uses viral vectors. Viral vectors are genetically engineered organisms that carry the gene of interest into the body. In Sputnik V, an adenovirus vector acts as a vehicle in delivering the infection causing SARS CoV 2 gene into the body. The vector does not integrate itself into the body cells. Instead, it releases the actual gene of interest into the body to trigger an immune response.
Adenoviruses are DNA viruses and cause acute respiratory infections, fever, and diarrhea in human beings. However, removing a part of the virus that is responsible for its reproduction makes this virus harmless. However, the body elicits a considerable immune response against the adenovirus as well. There are about 50 distinct variations of adenovirus (serotypes) affecting humans. Most of the vaccines use only a single adenovirus vector. Whereas, Sputnik V makes use of two serotypes (Ad26 and Ad5) of the virus.
The spike protein of the SARS CoV 2 is the preferred vaccine target among various other proteins – the reasons being, the spike protein mediates attachment and entry of SARS CoV 2 into our cells and it is the prime target of our immune response. It is isolated from the SARS CoV 2 genome and inserted into both the genetically engineered adenovirus vectors administered in two doses. The first dose comprises of Ad26 containing the spike gene. Second dose includes Ad5 in a 21-day interval.
This double vector approach has a significant advantage. On the administration of the first dose, the body develops antibodies against the Ad26 serotype. However, the second dose which contains the Ad5 serotype is still unfamiliar to the body. This stimulates the immune system to produce an enhanced immune response.
Poxviruses, alphaviruses are some of the other vector viruses. However, adenoviruses remain a popular choice owing to its advantages. Compared to other viruses, their genetic manipulation is quite simple and thus, large-scale manufacturing of this virus is possible. Further, DNA viruses like adenoviruses are less prone to mutation since they possess a proof-reading enzyme. They also have a relatively stable genome and are therefore safe.
On the flipside, adenovirus infections are generally common in humans. The presence of pre-existing immunity to the vector by previous exposure to the virus could make the vaccine less efficacious. So far, no licensed adenoviral vectored vaccines are available to prevent diseases in humans. Only one veterinary vaccine that uses adenovirus vector is available to date: the rabies vaccine.
Why a COVID-19 vaccine should not be rushed through?
Sputnik V has not yet undergone phase III trial which involves testing the vaccine in thousands of people. Several vaccines for various diseases have failed for many reasons. For instance, even after three decades of intense research, no vaccine exists to prevent HIV. Since the discovery of AIDS, many research teams trialed several vaccines. Nevertheless, none of them succeeded.
More recently, in February 2020, an HIV vaccine trial had to be terminated in phase III stage since it displayed low efficacy. The trial took place in South Africa and included 5407 young women and men. Unfortunately, 129 people inoculated with the vaccine and 123 people who were given a placebo developed an infection. South Africa has the highest incidence of HIV in the world and the fact that vaccinated individuals did not show a lower infection rate compared to the individuals given placebo indicated that the vaccine was not efficient in containing the disease. However, the exact reason for vaccine failure is not yet clear.
In 1966, a vaccine against the respiratory syncytial virus was available to the general population. The virus causes lower respiratory tract infections and it is almost fatal to infants. Even after completion of the trial, many children still contracted the disease, and even worse, two toddlers succumbed to death. It was only in 2008, the basis of the failure of this vaccine came to light.
The vaccine contained formalin to inactivate the virus. Inactivation was done to the extent that the critical antigens got disrupted and protective antibodies were not produced. The developed antibodies failed to bind to the real virus when the children were exposed. More specifically, the vaccine failed to trigger a signaling mechanism that helps the immune system recognize a virus and mount defense against it.
Dating back to history, various examples exist to explain the complexities in developing a successful vaccine. Moreover, given that viruses mutate frequently, it is even more challenging to develop a viral vaccine that would yield promising results. COVID-19 is a relatively new disease and there exists a knowledge gap with respect to the behavior of the virus. Though a vaccine is the need of the hour to combat the disease, rushing through its production before completion of trials, has inevitably given rise to skepticism.
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