One-dose SARS-CoV-2 vaccine policy may lead to antigenic evolution, study finds

As the threat of coronavirus disease (COVID-19) continues and in the face of vaccine dose shortages, several deployment strategies are being proposed to increase population immunity levels. Some countries have rolled out vaccination efforts to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.

In a new study, published on the pre-print server medRxiv*, an international team of researchers found that a one-dose policy may increase the potential for antigenic evolution. The study revealed that focusing on one dose may decrease infections in the short term, but longer-term outcomes rely on this immune strength.

Study: Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes. Image Credit: hedgehog94 / Shutterstock

Vaccine efforts

Since the coronavirus pandemic first emerged in late December 2019 in Wuhan City, China, scientists and pharmaceutical companies scrambled to develop COVID-19 vaccines.

To mitigate the spread of the illness, the deployment of safe and effective vaccines is essential. To date, 11 vaccines have been approved worldwide, including Pfizer/BioNTech, Oxford/AstraZeneca, and Moderna COVID-19 vaccines.

Pfizer/BioNTech and Moderna vaccines use the messenger ribonucleic acid (mRNA) molecules that encode the SARS-CoV-2 spike protein, with efficacy rates of over 95 percent, and 94 percent, respectively. Both these vaccines are provided in two doses.

Meanwhile, the Oxford/AstraZeneca vaccine uses a non-replicating adenovirus vector and has also been tested in clinical trials. It is administered in two doses, 28 days apart. In clinical trials, the efficacy rate of this vaccine ranges from 62 to 90 percent.

Since these vaccines have been distributed internationally, many countries such as the United Kingdom and Canada opted to delay the second dose to increase the number of people who will receive at least one dose due to the lack of doses available to each country.

Though there can be significant progress in boosting host immune responses in as many individuals, it is uncertain how strong and long the natural and vaccinal immunity is.

Description of the extended immuno-epidemiological model with one- and two-dose vaccination regimes (based on (8)). (A) Model flow chart depicting transitions between immune classes (see main text and Supplementary Materials for a full description of the immune classes and parameters). (B) Diagram of the inter-dose period (1/w ) considered between the first and second vaccine doses and its relationship to the rate of administration of the first vaccine dose v. The maximum achievable rate is v0 for a fully one-dose strategy, and v is assumed to decrease exponentially to its lowest value v0/2 when a fully two-dose strategy with inter-dose period corresponding to the clinical recommendation (Lopt) is employed. (C) Representative schematic of societal composition of various immune classes for the SIR(S) model with no vaccination (left), the extended model with a short inter-dose period (middle), and the extended model with a long inter-dose period (right).

The study

The researchers explored the epidemiological and evolutionary considerations with an extension of a recent immuno-epidemiological model for SARS-CoV-2 dynamics.

The team analyzed and studied the epidemiological impacts of the different dosing regimes on COVID-19 cases. They examined the potential impacts of dosing regiment via quantifying a time-dependent relative net viral adaptation rate.

Building from this, the researchers revealed that reducing the dose into one to cover more people will reduce infections in the short term. However, the long-term effect could pose a threat to antigenic evolution, which occurs when new variants or strains emerge.

Also called antigenic drift, it involves the genetic variation on viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that antibodies in humans recognize. This makes it easier and faster for the virus to spread in a partially-immune population.

“Under certain scenarios, we find that a one-dose policy may increase the potential for antigenic evolution. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose, and to ramp up vaccination efforts throughout the world,” the researchers wrote in the paper.

Emerging new strains

The world faces a new threat more than a year into the pandemic, new strains and variants. The recent emergence of several SARS-CoV-2 strains in still vulnerable populations highlights the evolutionary potential of the virus.

The United Kingdom first reported the new variant, called the B.1.1.7, in December 2020. From there, it has spread to many countries. In South Africa, another variant has emerged, called variant 501Y.V2, which contains the N501Y mutation.

With new strains and variants emerging globally, it is important to study if delaying the second dose can help reduce infections or promote antigenic drift.

To date, there are more than 106.45 million reported SARS-CoV-2 infections worldwide. Of these, over 2.32 million have died across the 192 countries and regions that have reported cases.

*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.

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.