Covid-19: variants and vaccination:
Tools to track variants and adapt vaccines as required

The three vaccines authorized in the UK for emergency use express the spike glycoprotein, the major target of neutralising antibodies in a natural infection. The vaccines protect against disease  and preliminary data suggest that transmission is also decreased after vaccination.

Current vaccines are based on a version of the spike glycoprotein from the start of the outbreak, however, and central questions remain around the ability of an old version of the spike glycoprotein to generate protective antibodies against newer emerging variants. Recent experts have suggested that variant of concern B.1.1.7 might be associated with increased mortality adds urgency to these questions.

A popular misconception, currently receding, is that SARS-CoV-2 mutates more slowly than other viruses. Genome sequencing of SARS-CoV-2 shows a nucleotide substitution rate of roughly 1×10-3 substitutions per year8—similar to that of Ebola virus.

The value of real time viral genomic sequencing was a major lesson from the Ebola virus disease outbreak in west Africa. Sequencing of SARS-CoV-2 occurs worldwide, but particularly in the UK, through the efforts of the COVID-19 Genomics UK (COG-UK) consortium. By conducting a continuous nationwide surveillance programme, almost in real time, the likely origin and spread of SARS-CoV-2 variants can be identified.

Considerable attention has been paid to changes in the spike glycoprotein and how these influence transmission dynamics and risk of immune escape. That  mutations seem to be associated with greater transmission suggests that spike variants should be monitored carefully as part of routine genomic surveillance, and also shows the need for studies to characterise the threat posed by potential mutations of concern.

Variants of concern might be associated with changes in both morbidity and mortality. Worse outcomes might be due to higher viral loads in infected individuals, altered transmission dynamics, or suppression of the host immune response. Some variants with deletions in viral genes that suppress the innate response are associated with milder infections but Challen and colleagues report evidence that a B.1.1.7 variant might be associated with an increase in mortality.

Protecting the future

Some countries will be slower than others to vaccinate their populations. SARS-CoV-2 and its variants will be around for some time, and concerns around the protection afforded by current vaccines will continue. The risk of immune escape is hard to predict long term, but we do know from experience with avian coronavirus that vaccines against one variant will protect against similar variants but not always against highly divergent variants.

Vaccines against SARS-CoV-2 will be needed for many years, and those vaccines will change as variants become too divergent, similar to vaccines agains influenza. National and global surveillance, together with well controlled assays to rapidly identify and characterise variants of concern, will allow us to move from current reactive approach to something much more proactive.

Covid-19: Officials query data from AstraZeneca’s US vaccine trial

Officials from the independent data and safety monitoring board (DSMB) overseeing AstraZeneca’s latest covid-19 vaccine trial have expressed concern that data released by the company this week may have been out of date and “provided an incomplete view of the efficacy data.” DSMB overseeing the trial told federal agencies and AstraZeneca that it was concerned about the information provided in the analysis. The National Institute for Allergy and Infectious Diseases responded by urging AstraZeneca “to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.”

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said  “ ‘headline’ estimates of efficacy being compared between trials is very unreliable. One explanation might well be that this trial is currently being conducted when there is a large amount of a new variant about more recently, and, as might be expected, the efficacy against that variant might be less, so more recent data shows reduced efficacy. Of course, the other vaccines may also show such reduced efficacy, and we don’t know by how much.”

“We will immediately engage with the DSMB to share our primary analysis with the most up-to-date efficacy data. We intend to issue results of the primary analysis within 48 hours.”