How can the existing vaccines against Sars-CoV-2 be used most effectively? For example, does it make sense to delay the second dose of the vaccine so that more people can get at least one dose? This is what researchers modeled in a study. Accordingly, this strategy leads to a reduction in infections in the short term, as more people are temporarily protected thanks to the first dose. In the long term, however, the risk of escape mutations could increase, the researchers warn.
The Sars-CoV-2 vaccines from the manufacturers BioNTech, AstraZeneca and Moderna are designed so that the vaccinees receive two doses at a certain time interval. This is the only way for the vaccinations to develop their maximum protective effect. A certain immunity arises from the first vaccination. However, this is likely to last less and less reliable. However, given the limited availability of vaccines so far, some countries, including England and Canada, have decided to delay the second dose in order to give more people at least one dose of vaccine.
How effective is the first dose?
Researchers working with Chadi Saad-Roy from Princeton University have now simulated the effects of this on the infection process using an epidemiological model. In their model, the researchers varied on the one hand how long and to what extent the first and second vaccine dose each protect against infection with Sars-CoV-2. On the other hand, they took into account possible evolutionary changes in the virus if some people have only partial immunity. Their models were based on the immunological data that are known about the previously approved vaccines from BioNTech / Pfizer, Moderna and AstraZeneca.
“In the short term, the distribution of single doses is beneficial and reduces the prevalence of the disease,” the researchers report. The long-term effects of such a strategy, on the other hand, strongly depend on how well and how long the first dose protects. “If the immunity is robust after a single dose, postponing the second dose is also optimal in the long term from an epidemiological point of view,” the researchers say. “Conversely, if immunity is weak after a single dose, the outcome may be more pessimistic.”
Risk of escape mutations
The risk of escape mutations is particularly relevant in this context. This is what immunologists refer to as genetic changes that make it easier for a virus to evade attacks by the immune system, for example through antibodies. This also harbors the risk that vaccines have a weaker effect. “The recent appearance of numerous Sars-CoV-2 variants in populations that are still relatively vulnerable underlines the evolutionary potential of the virus,” the authors write. In order for new variants to become established, two conditions must be met: On the one hand, such variants must result from a mutation. This is most likely in people with high viral loads, those with the lowest immunity. On the other hand, there must be a selection pressure that gives the new mutation an advantage. This is the case with people who already have some, but not complete, immunity, for example from the first dose of a vaccination.
As the modeling confirmed, the effectiveness of a vaccination plays a major role in how high the risk of developing or spreading escape mutations is. If the immunity is sufficient to ward off non-mutated variants, but not mutated ones, this promotes the spread of mutations. “In a scenario where full two-dose vaccination is highly protective while a single dose of vaccine provides less effective immunity, delaying the second dose could increase the risk of escape mutations,” the researchers said. The risk is slightly lower if the second dose is only pushed back slightly.
Further data required
Which of the simulated scenarios corresponds most closely to reality can only be answered on the basis of further data on the effectiveness of the first dose. Clinical studies to date have only provided very limited information on this. In the pivotal studies for the BioNTech and Moderna vaccines, although some participants dropped out after the first dose, the studies were not designed to assess efficacy in these circumstances. At AstraZeneca, on the other hand, various dose intervals were tested and there are initial indications that a greater interval does not impair the effectiveness and may even improve it. “Ultimately, the consequences of deviating from the dosage regimes prescribed by the manufacturer are still unknown at the population level, but will depend on the immune reactions,” said the researchers.
In the opinion of Saad-Roy and colleagues, as a basis for a responsible vaccination policy, further data are urgently required on how strong and how long the respective vaccine doses protect against people becoming infected with the virus and transmitting it. At the same time, the authors emphasize, their results underline the importance of the rapid global use of vaccines.
Source: Chadi Saad-Roy (Princeton University, USA) et al., Science, doi: 10.1126 / science.abg8663