COVID-19 Vaccine Research

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causal agent of the ongoing coronavirus (COVID-19) pandemic, has been evolving ever since the first outbreak in December 2019. Researchers believe that rapid vaccination is the most effective strategy to contain the pandemic. Adam Cunningham, professor of functional immunity at the University of Birmingham, said that, “Faster vaccination will ensure, a) the vaccinated individual is protected from the disease and b) vaccinated individuals do not transmit the disease, hence, the people around them are also protected.”

Dr. Soumya Swaminathan, chief scientist at the World Health Organization (WHO), stated that the main concern about some of the SARS-CoV-2 variants is that they have greater infectivity and can cause severe disease. She added that the vaccine manufacturers should keep a keen eye on the emergence of variants and study the mutation points. Accordingly, they should modify the vaccine structure regularly.

How do new variants emerge, and how do we track them?

Mutations may occur during the process of viral replication.  When a virus undergoes one or more mutations, it is referred to as a “variant” of the original virus. When a virus is rapidly being transmitted within a population, the probability of mutations increases. Most mutations have minimal impact on the character of the virus, i.e., its infectivity and symptoms. However, when mutations occur at specific genomic sites, they may change the main properties of the virus, e.g., the rate of transmission and the severity of the disease.

WHO is working with scientists and health officials across the world to understand the characteristic features of the emerging variants and their impact on both the authorized COVID-19 vaccines and those in development. This is carried out via the global SARS-CoV-2 laboratory network that includes the Virus Evolution Working Group. This group specifically focuses on identifying new viral strains and assesses their impact on the global population.

WHO has urged every country around the world to study the genomic sequence of SARS-CoV-2 extensively and share the results in public databases. This helps researchers and health officials to closely monitor, predict and make appropriate strategies to tackle the newly emerged variants in advance. Several research groups have analyzed the genomic sequence of SARS-CoV-2 and shared it via such databases, an example being GISAID.

Evaluating the effectiveness of the vaccines

WHO has established a SARS-CoV-2 Risk Monitoring and Evaluation Framework whose primary function is to identify, monitor and assess variants of concern (VOC). This team monitors multiple surveillance reports associated with COVID-19 and global research on VOC. Additionally, it determines the impact of the VOC on diagnostics, therapeutics and vaccines. The team also develops proper guidelines for vaccine manufacturers, such as the changes required in the vaccine design to maintain its efficacy against the VOC.

To evaluate the effectiveness of the COVID-19 vaccines, a group of researchers at the Columbia University Irving Medical Center examined all mutations in the spike protein. They created SARS-CoV-2 pseudoviruses, which comprise specific mutations similar to variants, such as alpha and beta. The sensitivity of these pseudoviruses is measured using the serum from patients who have received COVID-19 vaccines.

Effectiveness of the approved COVID-19 vaccines against SARS-CoV-2 variants

Dr. Zoltan Kis, a chemical engineer at the Future Vaccine Manufacturing Hub at Imperial College London, said, “Mutations can make the existing vaccines less effective, as these vaccines were developed against the “original” variant of the SARS-CoV-2 virus, and the new variants are slightly different.” Kis added, “Based on the data available so far, the reduction in the effectiveness of some vaccines is around 10% for these VOCs, so they are still effective.” However, he stressed that the effectiveness/efficacy values of vaccines lie on preventing symptomatic disease and the percentage values for vaccines preventing severe illness is even higher. According to David Ho, professor of medicine at Columbia University, the virus is travelling in the direction where it might evade the currently available vaccine-induced immune response. He further claimed that if more critical mutations occur, researchers might have to continuously conduct research to understand the newly developed SARS-CoV-2 variants, in a similar fashion to influenza virus research.

Ho and his colleagues have analyzed blood samples from people that received Moderna or Pfizer vaccines and found that these vaccines were less effective against two variants, namely, B.1.1.7 (alpha variant) and B.1.351 (beta variant). However, the Novavax vaccine was found to be 85.6% effective against the alpha variant.

WHO has reported that, to date, all the vaccines that have received emergency approval from various regulatory bodies around the world provide a certain level of protection against the new SARS-CoV-2 variants. This is because these vaccines are developed to trigger broad immune responses which involve the production of various antibodies and cells. Besides antibodies, the immune system produces two types of T cells, namely, helper T cells and cytotoxic T cells, that can eliminate viruses. The helper T cells or CD4⁺ T cells produce antibodies and cytotoxic T cells.  The cytotoxic T cells or CD8⁺ T cells seek out and kill cells that are infected by viruses. Studies carried out by Professor Alessandro Sette and his colleagues at the La Jolla Institute of Immunology at California revealed that individuals who have recovered from COVID-19 disease produce T cells that target at least 15-20 different fragments of coronavirus proteins. This poses difficulty for the variants to escape the immune system.

Is it possible to change the structure of the approved vaccine to increase its effectiveness against VOC?

Researchers have stated that if an approved vaccine is found to be ineffective against a SARS-CoV-2 variant, it is possible to modify its composition to offer protection. For instance, a manufacturer can redesign the vaccine by incorporating more than one strain in the developmental phase. Kis said that in the future, if the existing vaccines prove to be less efficient against VOC, manufacturers can rapidly use “technology developed during this pandemic (e.g., the mRNA vaccine platform) to design and manufacture vaccines against new variants and new viruses”.

“Many vaccine developers are looking into producing new vaccines to use a booster for the originally approved vaccines, these would incorporate the version of spike from the newer variants. These new vaccines will need to both maintain the immune response to the variants covered by the original vaccine, while providing additional protection against new variants,” said Professor Sarah Gilbert of the University of Oxford’s Jenner Institute.

Can vaccinated individuals still get infected with COVID-19?

It has been observed that even vaccinated individuals or people recovered from SARS-CoV-2 infection can still become infected with the virus. So, are the approved vaccines not efficient against some of the new variants? In this context, Gilbert said, “No vaccine against COVID-19 currently offers 100% protection, so it is possible that a vaccinated individual may get infected.” However, she added that vaccinated individuals are likely to contract mild disease. “The level of protection offered by a vaccine will also differ from one individual to another and depend on a complex range of variables including age, health status and genetics,” she said.