Where are we at with the fourth Covid Boosters?

Photo by Adam Gethin on Unsplash

It is currently the UK Government’s plan to give booster vaccinations this spring to people over 75 and those over the age of 12 who have some form of immunosuppression.  But what about the rest of us?

Vulnerable and elderly people struggle to mount a strong response to vaccines, however there is some evidence that more boosting could help them make enough antibodies to protect from severe illness, which is why they are first in the queue for boosters. Indeed, most recent data from one study in Israel shows a 78% reduction in death rate in people aged over 60 who received a fourth vaccine dose, compared to those who only had three. In younger, healthy people, the one study published so far shows that a fourth dose boosts waning immunity to similar levels as that of the third dose.

Vaccines are our best protection to date

It has been demonstrated time and again that having a complete regimen of Covid vaccination (two doses and a booster) can greatly reduce chances of becoming seriously ill, hospitalised or dying from a Covid-19 infection. Vaccines work and have a long history of proving so.

Vaccinations today are our main defence against Covid-19 and are keeping us out of further lockdowns. Yet, the simple fact is that the immunity given begins to wane from four to six months after injection. Practically speaking, that would mean boosting at least twice a year, which is not feasible nor sustainable. Perhaps a fourth booster would confer a longer lasting immunity, but that much is, at present, unknown.

Vaccines can be limited in their efficacy, owing to the development of new variants, as seen with the flu. H1N1 – the flu virus – first appeared in 1919 and over one hundred years later, we still get regular flu vaccines. This says a lot for how vaccinations must evolve alongside their target. Over the years, scientists have done much groundwork on tweaking flu vaccines to keep pace with the new variants, sometimes with efficacy success (55% in 2016) and other times not (15% in 2018). Therefore, a permanent vaccine fix for protection against Covid-19 is unlikely, at this stage, given the rapid emergence of variants and the vaccination doses currently in use. 

New Variants and Vaccine Technology

Covid-19 is set to follow a similar trajectory and challenge for scientists as the flu.  New variants are appearing in real time – as of this week we know of three variants of interest to the World Health Organization (XD, XE, XF) – and are still dealing with the dominant Omicron variants BA.1 and BA.2 in Europe.  But, having spent a long time chasing flu variants, scientists are ahead of the game with Covid in terms of vaccine technology.  As of March 2022, there are at least 96 vaccine candidates against Covid in development.  Furthermore, some laboratories are looking at an Omicron-specific boosters (Moderna).  

Other laboratories are exploring different methods of delivering vaccines, including one in a phase three trial that is being administered into the nose.  The rationale for an intranasal booster is that it could help to catch and neutralise the virus at its point of entry, before having the chance to infect its host and spread to other people.  A further bonus of this booster is that it is needle-free and easy to administer.

It is possible that we might have other options available for a fourth booster.  However, the development of medicines is a timely process: only one out of three vaccine candidates in clinical trials actually receive governmental approval for use afterward. This means it could be a long wait for an alternative booster. 

What about Covid immunity?

There is mounting evidence to demonstrate that prior Covid infection offers a defence against reinfection.  In a review of epidemiological studies of natural and hybrid immunity (the combination of prior Covid infection with vaccine immunisation), researchers found that protection against reinfections by natural immunity lasts over one year with only moderate, if at all, decline over this period. 

There are many reasons as to why it is difficult to compare protection inferred from prior infection to that of vaccination, but the message in this study is that vaccine protection appears to wane sooner than the protection offered in a Covid infection. This is why some governments will allow proof of recovery from Covid within six months as a ‘pass’ to travel. Yet, the most interesting observation of this study is that hybrid immunity was found to be the most effective way of preventing infection and severe illness as opposed to vaccines or prior infection alone.  The suggestion is not to go out and contract Covid – a bad idea for obvious reasons. Instead, given that one-third to half of the world’s population has been infected with Covid, this is a reminder that even in the face of recovering from Covid, vaccines are a valuable bonus. 

So, when can we expect a fourth booster?

Right now, the fourth booster makes sense for over 75 year olds and vulnerable people because of the new Omicron variants.  Boosting the immune system in this group can help raise their antibody levels and, if the data coming out of the Israel studies are accurate, a fourth dose is definitely beneficial for this group.

The government believes that the younger population can wait a bit longer. The return of spring means we will be outdoors more, where ventilation is greater and virus concentration in the air is low. Hopefully this means the trajectory of the virus will wane as the weather improves, as it did last year. Then, later in the year, other more essential boosters may become available.

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