Which strain should SARS-CoV-2 vaccine candidates target?

More than a year into the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several countries are beginning to roll out targeted vaccination efforts.

Under emergency regulatory body approval, countries like the United States and the United Kingdom have started administering vaccines to frontline workers and high-risk individuals. While the current vaccine candidates being used were designed to be multivalent and robust to emerging mutations, the potential for new strains to evade the immunizing response these vaccines are designed to elicit remains a significant risk factor in the current fight against the pandemic.  

A researcher at Clemson University, USA, has recently explored how governments might effectively combat the pandemic through strategic vaccination as new variants and strains of the virus emerge. The study suggests that vaccine candidates should target the fast-spreading variant, even when the initial prevalence is much lower.

COVID-19 vaccines

To date, the World Health Organization (WHO) reports that there are 235 vaccines developed against SARS-CoV-2. Of these, 63 are undergoing clinical evaluation or trials, while 172 are in pre-clinical development. A total of 15 vaccines are now in the last phase of human trials.

In the first week of December, following Medicines and Healthcare products Regulatory Agency (MRHA) approval, the United Kingdom has vaccinated over 130,000 people with the first dose of the Pfizer / BioNTech jab. In the first week of January, the second doses are to be given.

The UK’s Scientific Advisory Group for Emergencies (SAGE) endorsed the government’s move to pursue coverage of a high proportion of the population amid the surge of a new strain, which appears to be more infectious and fast-spreading.

Meanwhile, the United States has authorized and recommended two vaccines to prevent COVID-19 – Pfizer-BioNTech COVID-19 vaccine and Moderna’s COVID-19 vaccine.

Fast-spreading variant

Starting September, a new strain of SARS-CoV-2, named VOC 202012/01, has recently exploded across southeast England, prompting the government to impose lockdown orders once again in the region.

The new variant is deemed to be fast-spreading and up to around 70% more infectious, since it is a version of the virus with 23 mutations, eight of which are in the spike proteins, which is the part that the virus uses to attach onto and enter human cells.

The novel mutations include the N501Y mutation that allows the virus to bind more tightly to the human angiotensin-converting enzyme 2 (ACE2) receptor. It also has the D614G deletion that appears to make the virus more transmissible between people.

As of December 26, 2020, more than 3,000 cases of the new variant, which was confirmed by genomic sequencing, have been reported in the UK. The initial investigation by scientists confirmed that the new variant has increased transmissibility compared to previously spreading variants, but there is no observed increase in the severity of the disease.

Since December 2020, other countries have also reported cases of the new variant, including Denmark, Belgium, Germany, France, Ireland, Iceland, Finland, Italy, Netherlands, Portugal, Norway, Sweden, Spain, Australia, Hong Kong, Canada, India, Israel, Jordan, Japan, Lebanon, South Korea, Switzerland, and Singapore.

Another fast-spreading variant has been reported in South Africa, known as the 501.V2 variant. It is now the dominant form of the virus and has increased transmissibility. However, similar to the UK’s new variant, there is no evidence that the 501.V2 is tied to a higher severity of the infection.

The study

The study, published on the preprint journal medRxiv* server, shows that it is better for vaccines developed against SARS-CoV-2 to target the faster spreading strain, which could lead to surging cases in many countries.

Because the current vaccines developed were based on the previous strains of the virus, the study aimed to determine a solution for developing vaccines that can target the newest viral variant, or target the dominant but potentially less transmissible strain.

To arrive at the study findings, the investigator used a stochastic simulation to study how the choice of vaccine target affects outcomes of an outbreak of COVID-19 consisting of two different viral variants.

The study suggests that it is better to develop vaccines that target the variant that can spread more easily in populations. Even if the slower spreading variant is 100 to 1000-fold more prevalent at the onset of the vaccination period, targeting the faster-spreading strain is more effective.

However, the researcher also said that a mixed strategy, wherein 50 percent of the population receives a vaccine against one strain, and the other 50 percent receives a vaccine against the other strain, can perform well.

Overall, my model suggests that, except in very rare instances, monovalent COVID-19 vaccines should target the fastest-spreading strain of the virus, regardless of how prevalent that strain is at the outset of the vaccination period, and regardless of the degree of cross-protection offered by either vaccines or natural immunity,” the researcher concluded.

As the pandemic evolves, new strains of COVID-19 will continue to emerge that are more transmissible than the current variants. These strains may evade immune responses from the current vaccines being rolled out. Though this cannot be prevented, but governments can make strategic decisions about vaccination strategies to reduce surges of cases and save many lives.

To date, there are over 87.19 million COVID-19 cases worldwide. The death toll has topped 1.88 million people.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal references:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.


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