One step closer: a COVID vaccine designed for long lasting immunity

It took scientists less than 12 months from the moment the World Health Organization declared a global pandemic to develop a number of safe and effective vaccine candidates for COVID-19.
 
Expectations on multiple fronts were exceeded, with efficacy for some vaccines surpassing 90% thanks to previously unproven mRNA technology, helping to significantly reduce hospitalisation and death rates in highly vaccinated nations.
 
However, emerging global data has confirmed that efficacy tends to wane relatively quickly, with countries such as Israel, the United States and Australia now recommending a booster shot six months after the completion of the primary two dose schedule.
 
Booster programs are seen as somewhat of a luxury, given vaccination rates in some developing countries are hovering at just 10%. But what if there was a vaccine that resulted in longer lasting immunity that could provide protection for well beyond six months?
 
Scientists in Germany are one step closer to realising that goal, with the development of CoVac-1, a peptide-based vaccine candidate.
 
Unlike the current vaccines in circulation, such as those made by AstraZeneca, Pfizer and Moderna, which are designed to target B cells that generate antibodies against COVID-19, CoVac-1 targets T cells.
 
A phase 1 clinical trial, led by Professor Juliane Walz, to test the safety profile of the vaccine included 36 participants aged 18–80 years who were each given a single dose.
 
The findings, published in Nature on Tuesday, show that the vaccine is not only safe, but that after 28 days a SARS-CoV-2-specific T cell response was observed in all participants, with the effects persisting for at least three months. The T cell response also surpassed that induced by natural infection.
 
Dr Emily Edwards, who is a Postdoctoral Fellow at Monash University with expertise in immunology and primary immunodeficiency, told newsGP the findings are ‘extremely encouraging’.
 
When it comes to viral infections in general, she says the focus is always on antibodies with the T cell response often under recognised.
 
‘What is becoming more evident is that although antibodies protect from infection, it’s long-term memory, including both the B cells and the T cells, that protects against severe infection and deaths from the virus,’ Dr Edwards said.
 
‘We know that the antibody levels drop off, [so] what we want is that long-term memory that’s seeded in your immune system so that if you do come into contact with the virus – whether it be next month, next year or five years’ time – that that memory is there to spring into action to respond.’
 
Professor Stuart Tangye, a Research Director of Inflammatory Diseases (Immunology and Immunodeficiency) at Garvan Institute of Medical Research, says the vaccine appears to have a lot of strengths.
 
‘Whereas the current vaccines are really only using the spike protein as the major driver of immunity in vaccinated individuals, this vaccine covers proteins that are from other parts of the virus,’ he told newsGP.
 
‘So you get a broader immune response rather than putting all of your eggs into the spike basket.’


Dr Emily Edwards says it is encouraging to see COVID-19 vaccine research focusing on T cell immunity. (Image: Supplied/Samuel Noakes Photographics)
 
The trial findings also showed that the T cell responses were not altered by any of the variants of concern, including Delta, suggesting it could be equally, if not more protective than the current vaccines.
 
The prospect of CoVac-1 is of particular importance for people with B cell deficiencies, who do not make antibodies. While the current vaccines also generate a T cell response, Dr Edwards says it is to a lesser extent than CoVac-1, and therefore not as efficient.
 
So what would a vaccine like CoVac-1 mean for the global response to COVID-19?
 
Given that it is one dose and designed to induce longer term immunity, Professor Tangye says that if the vaccine does prove to be protective in later trials, it would be a convenient and accessible option, helping to overcome any supply chain issues.
 
‘It’s also a peptide-based vaccine with an adjuvant, so it shouldn’t have all the hysteria around “oh it’s a new type of vaccine, we’ve never had an mRNA vaccine before”,’ he said.
 
‘So for people who I’ve heard are hanging out for a different type of vaccine, it could ease those anxieties.’
 
However, both Professor Tangye and Dr Edwards agree that while promising, the vaccine is certainly not a panacea given the lack of focus on B cells.
 
Dr Edwards says that while targeting T cells is important, that alone is not enough to ensure infection rates drop and stay low.
 
‘The antibodies that you have circulating in your blood don’t need activation; they’re sitting there ready for if you get virally infected so they can respond almost straightaway,’ she said.
 
‘Whereas the memory cells have to identify that virus and then they will spring into action – the problem being that the infection rates are going to still stay high, but it will help with severity of infection more predominantly.’
 
The ideal scenario, Dr Edwards says, would be to have a vaccine that targets both attributes of the immune system, but admits that is ‘probably going to take a bit of tweaking’.
 
Professor Tangye agrees, and says the lack of an antibody response in the data is ‘quite striking’.
 
‘They showed only two out of 24 people in the second study developed detectable antibody levels, admittedly against the spike protein,’ he said.
 
‘And whilst they do pitch this as a T cell immunity vaccine, and centre it around being really good for people who are immunocompromised or don’t have B cells and so on, I still think you’re going to need to have an antibody response for some aspects of immunity against SARS-CoV-2 – there’s no doubt about that.’
 
What is a possibility, but remains unclear at this stage, is whether the vaccine could induce a better antibody response in those who have already received one of the current vaccines in circulation or who have had a natural infection.
 
‘What we have seen with the other vaccines is that when people who were infected with SARS-CoV-2 are then vaccinated, their antibody levels and their T cell responses after the first vaccine pretty much look like what you would see in someone who was double vaccinated but not infected,’ Professor Tangye said.
 
‘So this vaccine may work better for inducing B cells, for example, in someone who’s already vaccinated or even infected – we don’t know. That’s something that really should be tested.’
 
Despite the questions that remain however, Dr Edwards said there is no underplaying the importance of a vaccine like CoVac-1.
 
‘Particularly for those individuals where they’re not going to get a B cell response – which is more people than a lot of people realise – this is going to be so important to ensure that they are protected,’ she said.
 
‘We need to have multiple strategies in order to ensure that the bulk of the population is protected and that’s how we’re going to get the infection rates down, and that’s how severity of disease is going to get down.’
 
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