One vaccine will be good enough for all mutant strains of the novel coronavirus SARS-CoV-2, according to new research emerging out of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Australia.
India-born virologist Seshadri Vasan, who led the research work, says a single vaccine will also be effective for various geographic communities. This puts to rest fears that as the virus mutates or infects newer populations, more than one vaccine may be needed.
Vasan and his team provide the first experimental proof, backed by computer modelling, to suggest that changes to SARS-CoV-2’s spike protein, such as the ‘D614G’ mutation, are unlikely to affect the efficacy of vaccines in the pipeline.
“This is good news for the hundreds of vaccines in development around the world, with majority of them targeting the spike protein,” Vasan told Nature India . The novel coronavirus uses the spike protein to bind to ACE2 (Angiotensin-Converting Enzyme-2) receptors in human lungs and airways, the entry point to human cells.
Most COVID-19 vaccines under development — the Coalition for Epidemic Preparedness Innovations (CEPI) lists 321 — have been modelled on the original ‘D-strain’ of the virus, most common amongst sequences published early in the pandemic. Since then the virus had mutated to evolve new strains. As a result of the ‘D614G’ mutation, the virus evolved to a ‘G-strain’, which now accounts for about 85% of the published virus sequences globally; 86% from Australia; and 81% from India. (The D614G mutation is so called because it arises from an amino acid change from aspartic acid denoted by D to glycine denoted by G at the 614th position in the spike protein).
There have been speculations that the D614G mutation could have serious consequences. The first warning was sounded2 by Bette Korber at the Los Alamos National Laboratory as it began spreading in Europe in early February, and became the dominant form when introduced to new regions.
Vasan and his colleagues at the CSIRO, who have been closely watching the spread of this mutation, set out to answer an important question: will the efficacy of COVID-19 vaccines under development be affected, as they were using the sequence of the older D strain?
They tested blood samples from ferrets that had received a candidate vaccine against virus strains that either possessed or lacked this D614G mutation. "The study found no evidence the change would adversely impact the efficacy of vaccine candidates," Vasan said.
“We’ve also found the G-strain is unlikely to require frequent ‘vaccine matching’ -- where new vaccines need to be developed seasonally -- as is the case with influenza,” he adds. CSIRO chief executive Larry Marshall said in a press release that the research was critically important in the race to develop a vaccine. “This brings the world one step closer to a safe and effective vaccine to protect people and save lives."
Virologist and former professor at the Christian Medical College in Vellore T. Jacob John says that COVID-19, "being a single stranded positive sense RNA genome", is prone to mutations during replication and transmission to new host members. "Naturally our worry is if such mutations, especially in the spike glycoprotein gene, will cause antigenic drift that renders one vaccine not as efficacious as the other" he told Nature India .
Vasan and his team’s work very clearly documents that the well-known D to G mutation at position 614 of the spike does not alter the immunogenicity. “That is good news -- the study convincingly demonstrates antigenicity conservation in spite of mutation. What is true in ferrets should be true in humans too,” John said.
Globally the virulence of COVID-19 seems to be possibly declining, as suggested by gradual decline in case fatality rates in many countries. "The question that needs exploration is if the transmission efficiency is increasing and/or the virulence declining as a natural adaptation of a new virus in a new host”, he said.
1. McAuley, A. et al. Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2spike protein. npj Vaccines. (2020) doi: 10.1038/s41541-020-00246-8
2. Korber, B. et al. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 [Preprint]. bioRxiv (2020) doi: 10.1101/2020.04.29.069054