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Science Museum Group

Roger Highfield, Science Director, talks to the scientist behind the world’s first COVID-19 vaccine that requires only a single dose.

Johnson & Johnson, J&J, has shown the safety and efficacy of a single shot COVID-19 vaccine tested on 43,783 participants, demonstrating protection against COVID-related disease, hospitalization and death 28 days after vaccination.

Vaccines introduce inactivated coronavirus (or parts of the virus, from scraps of its genetic code to proteins) to the immune system of a person to train the body’s defences to recognise the virus as an invader so, if ever exposed to the actual virus, the body knows how to fight the infection.

In this case, the J&J vaccine uses a virus as a ‘vector’ to deliver the spike protein of COVID-19 into cells, training the immune system to recognise the pandemic virus and protect the body.

Made by J&J’s Janssen Pharmaceuticals division, the company has signed an agreement with UK Government for 30 million doses on a not-for-profit basis for emergency pandemic use, subject to regulatory approval.

I talked to Dan Barouch who helped developed the vaccine, Director of the Center for Virology and Vaccine Research at the Beth Israel Deaconess Medical Center,  Boston.

His edited answers are shown in italics.

HOW EFFECTIVE IS YOUR ONE-SHOT VACCINE?

The efficacy is lower than the top-line numbers reported from Moderna and Pfizer, which was 94/95% efficacy.

But you have to realize that the Pfizer and Moderna studies were done last fall at a time when the pandemic was simpler and there were fewer variants.

The results published on the J&J vaccine a few days ago show a high level of protection against the pandemic in the here and now, right where we have a much more complex pandemic now than we did three or four months ago.

Not only is the surge of so-called force of infection – the rate at which susceptible individuals get the disease – much higher, but we have multiple viral variants circulating all throughout the world, including in the United States, which accounted for the California surge, and in Brazil and South Africa and in the UK.

Some of these variants lead to a higher degree of transmissibility and contagiousness. And some of these variants are actually partially resistant to antibodies.

All three of those factors would make any vaccine show lower efficacy today than it would have several months ago. We know from the Novavax data (this consists of a laboratory made version of the viral protein with an immune-boosting adjuvant) that the Novavax vaccine showed decreased efficacy for this so-called UK strain compared with the original strain in the study in the UK and a marked reduction of efficacy in South Africa.

So, comparing studies done last fall with more recent studies is like comparing apples and oranges. There is really no head-to-head data comparing the efficacy of these vaccines.

Data from Israel show that vaccines can curb COVID-19. However, South Africa has paused its roll-out of the Oxford-AstraZeneca vaccine after a study showed “disappointing” results against its new COVID-19 variant, and its government will offer vaccines made by J&J and Pfizer.

HOW DOES THE ONE-SHOT VACCINE PERFORM?

Our vaccine offered or provided 85% protection against severe disease, not just the US but also includes Latin America and South Africa, with a huge force of infection and against the resistant variant. Our vaccine also showed 100% protection against hospitalization and death.

You have to ask what do you want a vaccine to do? Do you want it to prevent the sniffles, or do you want the vaccine to prevent you from getting sick? We could offer the latter, and with a single dose when we are already getting obsessed with the logistics of the second dose and all that.

HOW DO YOU KNOW ONE DOSE IS ENOUGH?

Our vector has been chosen to be highly immunogenic with a single dose and I think we’ve seen we’ve seen the power of a single dose vaccine in the study’s results.

Think of all of the political debates, the logistic challenges that we have in the Western world with a two-dose vaccine and amplify that orders of magnitude in the developing world.

By contrast, a single shot vaccine that does not require sub-zero freezing, is logistically a much more implementable vaccine for both the Western and the developing world, and offers substantial protection, particularly against severe disease. 

WHAT DOES YOUR VACCINE CONSIST OF?

Our vaccine with J&J involves a deactivated common cold virus called an adenovirus. We use a human adenovirus called adenovirus serotype 26 (Ad26) which is designed to make the SARS-CoV-2 spike (S) protein.

By comparison, the Oxford AstraZeneca vaccine is based on a chimpanzee adenovirus that they call ChAdOx1 and is a two-shot vaccine, whereas our vaccine with J&J is a single shot vaccine.

The Russian vaccine, Gamaleya’s Sputnik V, is also based on the Ad26 virus, based on academic work that our group published from 2003 to 2010.

In their case, the second booster shot is another human adenovirus, adenovirus 5 (Ad5) which also carries the gene for the SARS-CoV-2 spike protein.

When we started our adenovirus vector work in around 2003, most groups in the world were using Ad5 as a vaccine vector. That’s very potent, but the problem is that many people have high levels of baseline antibodies against the vector itself, since Ad5 is a very common cause of the common cold.

What was not known at that time is that many people in the developing world had such high levels of antibody that they were sufficient to suppress a vaccine based on Ad5. That is why we started a project in 2003 to develop other adenoviruses, looking at Ad26 and a dozen other types.

HOW LONG DID IT TAKE TO DEVELOP?

My group at Beth Israel Deaconess Medical Centre initially cloned and vectorized (copied and turned into a carrier of a viral protein) between 2003 in 2007 as part of our programme to develop a vaccine against HIV, which we took into animal studies, then conducted the first in human clinical trials and large-scale clinical trials for HIV, which are still under way.  

So, if it were not for our HIV research programme, we would not have an adenovirus 26 based COVID-19 vaccine today.

HOW DID YOU MAKE THE ADENOVIRUS SAFE FOR A VACCINE?

Similar to other adenovirus vectors, we have taken out the replication machinery so the vector cannot replicate in human cells at all.

We grow the vector in specialised human manufacturing cells that provide the proteins needed for the replication of the virus. So, in scientific talk, we say it trans complements our Ad26 vector, which does not have any replication machinery. Once purified then it can’t actually replicate after injection in your arm.

WHAT DO YOU MAKE OF THE ARGUMENT ABOUT DELAYING THE SECOND DOSE?

The UK decision to delay the second dose of the Oxford and Pfizer vaccines has divided the medical community. Fundamentalists argue that vaccines should be delivered in the same way as they were tested in trials. Pragmatists argue that to delay the second dose more people can be given protection more quickly. When it comes to the Oxford vaccine, for example, there is some evidence that delaying the second dose to 12 weeks increases protection.

I agree with both and that’s why I think the solution to the question is that a single dose vaccine that has proven efficacy and proven durability is superior because it essentially obviates both the logistics of the second dose.

The swirling debates come to instil in an era of vaccine scarcity. We do not have enough doses to vaccinate the entire population in the US in the UK let alone the population of the world. However, with a single shot vaccine, then the vaccine supply just goes twice as far.

J&J is committed to providing a billion doses of vaccine during this calendar year, that can protect a billion people.

Oxford University has launched a study that will mix and match two COVID-19 vaccines – the Pfizer and AstraZeneca vaccines – in a bid to simplify the logistics of immunizing millions of people — and potentially boost immune responses in the process. Vaccine developers often combine two vaccines to combat the same virus, and researchers are keen to deploy the strategy — which the experts call a ‘heterologous prime-boost’ — against the coronavirus.

DOES YOUR VACCINE PREVENT THE VIRUS FROM BEING TRANSMITTED?

We have not done those studies yet because our efficacy trial only came out a few days ago. But clearly, that is an important question.

It has been widely reported that the Oxford vaccine reduced positive readings for the virus by 67% after a single dose, and 50% after the two dose regimen, suggesting a substantial impact on transmission of the virus.

This study was not a transmission study, and thus no statement can be made about blocking transmission.

HOW IS THE WORLD DOING?

We are now close to the one-year anniversary of the COVID-19 pandemic, plus or minus a month, and we have seen the development of not one but multiple vaccines – at least two RNA vaccines, three adenovirus vector-based vaccines, a protein-based vaccine and one inactivated virus vaccine.

There are more, and the fact that the global research community has developed, proven safety and efficacy, and done rollouts of multiple vaccine candidates in a year is a remarkable scientific accomplishment. I would give equal credit to all the groups.

But I would add that it shows the success of basic scientific research. Vaccinology has taken a great leap forward over the last year, but it was only possible because of the less well publicized scientific advances in immunology and virology and vaccinology over the last 20 years.

What we’re seeing is as the successful development of multiple COVID-19 vaccines by multiple groups and multiple companies in record time essentially represents the culmination of decades of scientific advances over time. And that is, I think, an astonishing feat.

TELL ME ABOUT THE HIV RESEARCH THAT MADE YOUR VACCINE POSSIBLE

Most people in research know me as an HIV vaccine developer. So, I can talk to you for as long as you like about AIDS.

Apart from the challenges of variants, COVID-19 is more of a well-behaved virus than HIV.  

When it comes to HIV, we have encountered scientific challenges that are truly unprecedented in the history of vaccinology.

There is vast sequence diversity so you are not developing a vaccine against one virus. You need to develop a vaccine against millions of viruses simultaneously.

HIV surface protein is covered with sugars, and so it’s very hard to be recognized by antibodies, and it’s very difficult to induce these antibodies. The virus also targets the immune system, killing white blood cells called T cells.

There is no immune correlate of protection and by that, I mean not a single person that we know of has cleared HIV based on their own immune responses, so we actually don’t even know those immune responses have the capacity to prevent or clear HIV infection, let alone know exactly what they are.

And, HIV integrates into the host DNA very quickly so a vaccine has to act very, very quickly to stop the viral genetic code getting into the patients.

Many vaccines act only after there’s some level of virus replication for HIV. If there is any virus replication at all, the virus will probably have integrated into the host chromosome leading to lifelong infection that can resurge at any point in time.

Vaccinology has never had to contend with all those challenges before. The good news is that if it weren’t for our HIV vaccine program, then there would be no Ad26 J&J vaccine because the fundamental vaccine technology would not have existed.

WILL THE RISING NUMBER OF VACCINATED PEOPLE LEAD TO NEW STRAINS?

The introduction of vaccines will increase selection pressure and could result in the virus mutating. However, by cutting down infection rates, that will also decrease the chances, so I think that as long as the vaccines are successful in reducing viral infections, then it overall will reduce the risk of emergent variants.

HOW EASY IS IT TO MODIFY YOUR VACCINE TO DEAL WITH NEW STRAINS?

Many teams are now working on vaccines to target the mutations, for instance, the RNA vaccine under development in Imperial has announced this will be its focus, Oxford is working with AstraZeneca to prepare for a strain change, Moderna is working on a booster to deal with the South African variant, and so on.

It’s really a matter of just making a few small changes to the spike sequence we use in our vaccine. It would require the generation of a new product, so that does take a couple of months. But new gene-based vaccines such as the RNA vaccines and the vector-based vaccines are actually well suited for updates. Although a relatively minor change can be done relatively quickly, it’s not trivial because it will be a new product that must follow Good Manufacturing Practice.

But it’s certainly not the same as starting from scratch.

SHOULD WE BASE VACCINES ON OTHER COVID PROTEINS THAN THE SPIKE?

There should be more research on this. I think everyone picked the spike protein to start with, but we know there are strong T cell responses against the virus’s membrane and nuclear capsid proteins, so it would be a study to investigate whether the addition of one of the other proteins to the vaccine might add to the protection.

But it’s unclear whether it’s needed and it unclear whether it will help, but certainly, the hypothesis is that it might be able to improve these vaccines.

HOW WORRIED ARE YOU ABOUT VACCINE HESITANCY?

What we saw last fall, unfortunately, was that vaccine research, which typically doesn’t get a lot of public attention, was widely publicized and became intertwined with American electoral politics.

Because of how divided our political system has become, at least in the United States, we saw vaccine hesitancy really go up to peak levels. That was also before we had safety and efficacy data for any of these vaccines.

Now two things have changed: the vaccine research field is no longer intertwined with electoral politics because the election is over and, secondly, we have safety and efficacy data for multiple vaccines: Pfizer, Moderna, AstraZeneca, J&J and recent data from Novavax too.

These data say these vaccines are safe and they are effective. And that is unquestionable because these are randomized trials with placebos and controls.  These vaccines are proven to be safe and proven to be effective. And it’s not only politicians saying that is the case, it’s the doctors and the scientists and developers.

What we’ve seen, at least in the United States, is that vaccine hesitancy has started to decline. It’s still not where we need it to be, but I believe that vaccine hesitancy will continue to decline as there is further outreach and education aimed at the general public.

The Science Museum is holding an event later this month to discuss vaccine hesitancy with Dr Anthony Fauci, Chief Medical Advisor to the Biden administration, Professor Beate Kampmann, Director, The Vaccine Centre, London School of Hygiene and Tropical Medicine, Dr Doug Brown, Chief Executive, British Society for Immunology, Professor Heidi Larson, Director, the Vaccine Confidence Project and Nadhim Zahawi, UK Minister for Covid Vaccine Deployment.

GIVEN THE NEW STRAINS, WILL WE NEED AN ANNUAL COVID JAB?

It depends on what happens with the pandemic during this coming year. What we do now as a global community is extremely important. With the recent data showing that vaccines still have substantial efficacy against the variants, I think that we still have a chance at eliminating the global pandemic.

However, that will require a substantial increase in the pace of the vaccine rollout, both in the Western world and throughout the globe. If we do that, we might still be able to get the current pandemic under control this year with the current vaccines. But we won’t if the vaccine rollout is slow and we’re unable to vaccinate the global population.

There remain large areas of uncontrolled virus replication. Then we might see the emergence of variants that will necessitate new vaccines and we might be in an endless cycle of new variants, new vaccines, new variants, new vaccines, as is the case already with influenza. So, what we do this year in terms of how effectively and how rapidly we can implement the vaccines throughout the world this year is critically important in whether we are able to control the pandemic or not.  

We have the tools. Now we have to use them.

HOW CAN I FIND OUT MORE?

The latest picture of how far the pandemic has spread can be seen on the Johns Hopkins Coronavirus Resource Center or Robert Koch-Institute.

You can check the number of UK COVID-19 lab-confirmed cases and deaths along with figures from the Office of National Statistics.

There is more information in my earlier blog posts (including in German by focusTerra, ETH Zürich, with additional information on Switzerland), from the UK Research and Innovation, UKRI, the EUUS Centers for Disease ControlWHO, on this COVID-19 portal and Our World in Data.

The Science Museum Group is collecting objects and ephemera to document this health emergency for future generations.