Universal Vaccines – The Lowdown

An interesting news item appeared last week in the BBC News Health column.  As someone with an active interest in vaccine development it certainly attracted my attention, and I think it merits some discussion as a possible 'game changer' in our approach to preventing human disease….

The concept of a ‘Universal’ vaccine has been in the minds of those in the vaccine development field for many years, but the recent announcement is the first suggestion that such an intervention might actually be possible…and effective.

I should add straight away that the Stanford research project is still very much in its early stages and positive results have only been shown in lab mice to date. The methodology is nowhere near entering human trials yet, and this will be the only way to demonstrate whether a more universal approach to vaccination would be viable in humans. Immunity is a lifelong process, and apart from anything else, the difference in lifespan between humans and mice raises a major question about the longevity of any ‘universal’ effects, and the implications they might have on our long-term acquired immunity.

How would ‘Universal vaccination’ actually work, and how does its mechanism differ from conventional vaccines ?

First, we need to look in more detail at how the ‘conventional’ vaccination approach works. 

This relies on administering ‘foreign’ material, derived from a pathogen of interest (usually by intramuscular injection) to challenge the immune system. (The newer mRNA vaccines go about this in a slightly more roundabout way, by providing a genetic message to the muscle cell in the from of an RNA strand, and this causes it to produce the antigen internally; the end effect is the same, i.e the introduction of a foreign antigen). The presence of this antigenic material somewhere it shouldn’t be (i.e. in your arm) stimulates the immune system to mount a response. This includes production of both T cells and ‘humoral’ (i.e. non-cellular) antibodies, both of which are highly specific for the antigen and can recognise it. These then latch onto to the antigen specifically whever it is encountered, and by doing so, effectively ‘flag’ it for destruction by a whole 'cohort' of other immune cells we all have at our disposal to do the 'heavy lifting' of dealing with the invader.

Thus immunisation ‘teaches’ the immune system to recognise (and hopefully destroy) a specific pathogen, and this immunity is retained over time to help us respond quickly to, and combat , any future infections. This ‘learned’ response is termed ‘acquired’ immunity and is key to our survival.

It is not the whole story of our immune defence mechanism, though – fortunately for us, we also have what is arguably an even more important line of defence in the form of what’s called ‘innate’ immunity. This is what kicks in as soon as we are infected by a pathogen which we haven’t met before and to which we therefore don’t have any acquired immunity. 

The innate pathway is essential for our short term survival in the face of a new and unknown infection, since it mounts an immediate response in the absence of prior experience of the pathogen. It is also the innate pathway that is utilised by our ‘Universal’ vaccines.

The innate immune system is always present, but normally exists on standby, remaining ‘on watch’ i.e. on the lookout for anything it thinks is foreign and could present a threat. Specific 'self' recognition factors normally stop it attacking to our own tissues, and it is only ‘mobilised’ into action when it detects an external threat.  However, even the innate system does take some time to activate, and the system may respond weakly, or even not at all, in some circumstances (e.g. immunosuppression, immune  decline in old age, or immune ‘concealment’ via the checkpoint mechanism as in the case of cancer cells.)

Universal ‘vaccines’ would be designed to bypass this initial response activation step by providing an initial stimulus to the innate immune system. The Stanford prototype vaccine adopts a 3-pronged approach with two existing drugs utilised tostimulate one of the innate system's 'sentinel' cell types, the macrophages, while a tird compoenet stimulates a specific population of T cells into action. This combined stimulas mobilises the innate system ready for prompt action, but does so in the absence of any specific threat. 

(As an aside, the term ‘vaccine’ is arguably a misnomer here in that no specific antigen is present, and the stimulus is a non-specific one, but the term will probably stick anyway. I suspect Jenner will probably not be turning in his grave at the inaccuracy, though, given the tribute to his work afforded by humanty's dependence on the conventional vaccination principle he discovered).

The key difference between the two approaches is thus in the breadth of the stimulus, with the Universal vaccine effectively ‘pre-activating’ the innate system against all comers, allowing a faster and more effective response to any foreign 'invaders' rather than just one specific type.

The Stanford report in the Science journal claims up to 1000-fold reduction in viral or bacterial uptake following an infection challenge with a wide variety of viruses, bacteria and even some common allergens.

What’s not to like, you may ask ? How quickly can I get some of this wonder product ?

Inevitably with an early discovery such as this there are important questions to ask…and answer before we rush into developing and using it.....

The Down-side

Firstly, there are some concerns about the effects of over-stimulating a system that’s designed to work only when it’s actually needed. An ‘always on’ status will likely generate stress in any system (as many of us are finding out at work or on social media), and could make it less able to respond effectively in a crisis.

The other major question is whether continual activation of an otherwise normal immune system would increase the likelihood of auto-immunity. (This is the term used to describe one of the many conditions where our own immune systems respond to ‘self’ i.e. start to attack our own tissues and organs, sometimes with devastating results). Experiments in a small short-lived rodent species such as the mouse (or indeed even in larger animals) could not possibly answer this question, and a definitive answer can only come from human clinical studies.

There's also the technical issue of access to the target tissue. Intranasal administration, although effective in the mouse, might not be adeqaute to protect the lungs in humans due to the length and extent of our bronchial tree. Thus nebuliser dosing might be required to achieve adequate penetration.

Last, but not least, is the question of how long-lasting the effects of each administered vaccine dose would be. The mouse experiments with an intra-nasally dosed vaccine seemed to indicate an effect persistent out to ca 3 months. This could be useful if reflected in human subjects, but would require more frequent boosting than is normal for conventional vaccines. 

I should emphasise here that, by stressing possible snags with the approach, I'm not in any way belittling the achievement. It could be a real game changer if we can identify, and then circumvent, any potential 'show stoppers'. And the concept isn't a new one - we have been using the Bacillus Calmette-Guérin (BCG) vaccine, most notably against that perennial menace, the tuberculosis mycobacterium, and have shown that it provides non-specific immunity in a number of different scenarios against a range of other diesase by changing the nature of the immune cells responsible for our innate system. Thus the approach does already have 'form' for effective non-specific protection in the human without causing significant harm.

How would a universal vaccine work in practice ?

We would probably not such a tool to work in isolation, but rather as a supplementary defence in conjunction with conventional vaccination. 

Thus, the primary goal of a universal vaccine initially would be as a 'holding-operation', acting as a deterrent and allowing the immune system to fight off a range of seasonal infections during the ‘respiratory season’. It could also be used to reduce the initial viral burden in the early stages of a pandemic pending the development of a specific conventional vaccine against the new pathogen, thus potentially saving lives and reducing the need for self-isolation and lockdowns.

If such a therapeutic approach were proven to be both safe and effective, its key advantage would be its very non-specificity. We are plagued by legions of different respiratory viruses on an annual basis, the vast majority of which are currently ‘un-vaccinatable’ i.e. too nimble and ‘fleet of foot’ in evolutionary and mutational terms for us even to contemplate going to the lengths of developing a specific antigen vaccine against any one of them, let alone sequencing its genome, which we would need to do to produce an mRNA vaccine.  An effective universal vaccine might actually protect us from some of these perennial, and often debilitating, pests.

Who knows…that universal panacea and 'holy grail' of the pharmaceutical world, a cure for the common cold, may actually be nigh !....

First published:  22.2.26