1. What are second- and third-generation vaccines?
In response to the original strain of SARS CoV-2 a first generation of vaccines was developed, tested and rolled out. This includes the Pfizer-BioNTech, Moderna, Oxford-AstraZeneca and Janssen vaccines. We have been very fortunate that they have proved highly effective.
These vaccines can now be improved in a variety of ways and adapted to what the needs are – this would lead to second- and third-generation vaccines.
With the second generation, scientists are trying to adapt the current vaccines to the new and emerging variants of the virus.
Thinking further down the line, third-generation vaccines will be about managing Covid-19 long-term. Within three to five years, scientists will be looking at developing vaccines which cover and protect against multiple variants of SARS CoV-2, and even against multiple coronaviruses.
Charlie: When I think about the different phases or generations of vaccines, you’ve got, for Covid for example, you’ve got the current vaccines that are licensed now, the front runners. And I will call them the first generation.
You’ve then got the next wave or generation of vaccines, which is trying to adapt the current vaccines to the new variants to make them expand their targets to cover the next variants.
And then you’ve got, thinking down the line a little bit to maybe the third-generation vaccines, about how do we manage Covid longer-term, thinking three to five years. How do we develop vaccines which cover multiple variants, or which cover and can protect against multiple coronaviruses?
It’s important to evolve and adapt the vaccines to what the need is.
2. What benefits could new generations of vaccines bring?
With improved vaccines we may be able to improve the effectiveness of global vaccination, and make sure that people everywhere in the world, including children and those who are clinically vulnerable, are protected.
Scientists will be looking to make Covid-19 vaccines which:
- are easier to store: vaccines can be made more thermostable, meaning they remain effective even in extreme temperatures, or there is less of a need for cold chain freezers and fridges. This would cut costs down for many countries.
- are easier to manufacture: over time the amount of active ingredients can be adjusted, ideally to the minimum required to achieve immune protection. This has the potential to improve vaccine supply if fewer raw materials are needed.
- can protect against new variants: so far, our first-generation vaccines are proving effective against the variants which have emerged recently. However, research needs to continue so that vaccines can be adjusted to respond better to existing variants, and to be effective against new, as yet unknown, mutations of the SARS CoV-2 virus.
- can provide broad, long-term protection: we don’t yet know how long immunity from first-generation vaccines will last. Research needs to continue to establish ways of measuring our immune responses, so we can find proxies for immunity – what are known as ‘correlates of protection’.
- can act as a universal coronavirus vaccine: it may be possible to create a vaccine that protects against all SARS CoV-2 variants and other coronaviruses.
3. What do we still need to learn about Covid-19 and vaccines?
We have learned a huge amount about what was previously an unknown virus. We now know that by targeting the spike protein of SARS-CoV-2, multiple vaccines can produce a strong immune response against the original virus – this was not a given.
And we have made advances in vaccine ‘platforms’ like mRNA and viral vectors, which means we are better placed to adapt the vaccines we have to future variants.
But there are still many unanswered questions. For example, how long will vaccines provide protection for: one year, two years or longer?
By knowing this, we may be able to make current vaccine supplies go further. If we can agree that booster doses are not needed in the near future, doses that high-income countries have reserved for such programmes could be made available to other populations.
There are also important questions about the impact of the vaccines on transmission. And whether the licensed vaccines are effective on adolescents, children, immunocompromised people or pregnant women. This information is starting to come in – for example, some countries have already decided to vaccinate children over the age of 12 based on the existing data.
These are all important questions for understanding what we can improve with new generations of Covid-19 vaccines.
4. What do we need to do to make vaccines as successful as possible?
The rapid development of the first generation of Covid-19 vaccines has been a landmark moment for the speed at which we can create vaccines.
We were able to move so quickly because of decades of investment in discovery research. That’s what enabled the mRNA and viral vector technologies to be progressed to a stage that they were ready to respond to Covid-19.
Public, private and philanthropic collaboration on a global scale and financial investment on a never-before-seen level have also played a crucial part.
But now international funding is not keeping pace with global research needs.
The ACT-Accelerator needs an investment of $16.8 billion this year to get lifesaving tests, treatments and vaccines from the laboratory to the front line in the countries that need them most.
And it’s not only about money, because at this point money can’t buy vaccine doses that don’t exist. The available global manufacturing supply for this year is already spoken for.
The vast majority of vaccinations so far have been in only a few rich countries. Now wealthy nations that have secured multiple deals with vaccine manufacturers need to start sharing doses with those most in need globally.
This is the quickest way to end the pandemic and reach the most vulnerable people everywhere.
Special thanks to Anna Mouser, Policy and Advocacy Lead, Deborah King, Vaccines Research Lead, and Divya Shah, Epidemics Research Lead at Wellcome, for contributing to this article.