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The Virus’s Gambit: The vaccine response

Maverick Citizen

Maverick Citizen Op-Ed

The Virus’s Gambit: The vaccine response

(Photo: timesofindia.indaitimes.com / Wikipedia)

For perhaps a month, we had the naivete to think that with the high vaccine efficacy of both the Moderna and Pfizer vaccines, we were ahead of this virus. Sitting pretty, so to speak: 95% effectiveness in overall disease and nearly 100% efficacy in preventing severe disease. We just needed to pump out vaccines and all would be well. This illusion – I’ll now call it delusion – has now abruptly ended.

The bubble burst thanks to the scientific prowess of our South African brethren, who had the foresight to set up a surveillance system in a very systematic, regionalised way to see how the virus was mutating. 

This is the way molecular epidemiology and pandemic control should be undertaken. They detected incredibly sudden changes in the virus’s mutational pattern – not single changes, but multiple changes in several areas of the spike protein. 

These changes were in regions of SARS-CoV-2 that we had not seen before, and were “dangerous” for our current vaccine strategies because the mutations were in the receptor binding domain (RBD), which defines the part of the spike protein where the virus attaches and to which neutralising antibodies are directed. 

Some of these mutations looked like they might not be accessible or resistant to the neutralising antibodies that arise after natural infection or even vaccination. And there were changes in another area we call N-terminal domain (NTD) that we don’t really understand, but we know that some monoclonal antibodies that neutralise could be identified in that region too.

The South Africans reported these changes to the United Kingdom because the predominant strain in South Africa in the early parts of the epidemic was similar to the one in the UK, something one would expect with the large international travel between the two countries. 

This led UK molecular biologists to look harder at strains circulating in their country, and again they found a new variant that was starting to sweep over the country and create a second wave that we now see with increased rates of transmission and increased rates of hospitalisation. 

This variant had one of the mutations in the RBD part of the genome, the one that appears associated with increased replication in the nose and transmission to other people, but fortunately not the changes that alter the neutralising antibodies.

Very quickly, scientists put two and two together and they saw two things were happening: the virus was evolving more rapidly than previously detected and was in two behavioural characteristics, and these two characteristics were being detected in the same virus. 

The UK variant had a change in one area of the RBD gene that increased the ability of the virus to attach to its receptor in the human body, and scientists were finding it replicates faster in cells and has a higher rate of replication in the nose and subsequent rate of transmission. 

We had seen that behaviour back in June when we had a variation in the US where the original strain from Wuhan was overtaken by what we call the D to G614 strain; that’s what is mainly circulating here. 

This strain also increased attachment, but the F105Y mutation enhances these characteristics even more and the spread seems to be even greater. 

This UK strain is now called the B.1.1.7 strain, which has spread throughout Europe and is being increasingly recognised in America. The CDC predicts that this strain will be the predominant one in the US over the next few months. 

The South African variant, now called B.1.351, also has the increased transmissibility gene of F105Y, but in addition to the UK variant has a couple of nasty mutations – one called E484K that is associated with escape from an important neutralising epitope that most people have after contracting Covid-19 and is also induced by vaccination.

This mutation has been seen in other unrelated strains, so it seems to be a frequent way the virus tries to use to escape from people who have acquired immunity.

So, people who have been infected with prior strains and developed immunity to those prior strains appear to be at risk for the virus strains that have the mutations from South Africa. 

We call this escape from neutralisation or adaptive immune escape from the virus’s point of view. This is what RNA viruses do: influenza does this; HIV, of course, does this too. 

In retrospect, we were a bit naïve about SARS-CoV-2, thinking that because this subgroup of coronaviruses edits its mutations more efficiently, we might escape having lots of different strains. 

But natural selection is very powerful, as Darwin taught us. 

What we have now is more people having SARS-CoV-2 infection than ever before on earth; and it’s ever-increasing. 

This is exacerbated by more interactions between people because we’re tired of physical distancing; and by more people with past infections who have antibodies that force the virus to escape. So we find ourselves in a situation where, mathematically, this is not going to stop. 

What do we do about it? 

This week brought us data that says, yes, we do need to manage this, but we don’t have to panic. We have evidence that our current tools are going to be okay, but we have to create strategies to get us back up to the optimal state. 

Second important concept: vaccinating everyone globally is going to be necessary to stop the spread. What impacts on one of us impacts on all of us. Ongoing community spread anywhere with this virus means spread everywhere.

We now have hard clinical evidence that our current vaccines will work as well against the UK variant as they have against the variants circulating in the US. 

The best evidence of this is a 14,500-person clinical trial of the Novavax vaccine, which showed a 90% efficacy rate in a UK study where the UK variant constituted 30% to 40% of the strains circulating at the time of the trial. 

The antibody concentration from this two-dose vaccine is pretty similar to what we saw in the Moderna and Pfizer vaccines, and several groups have now shown that sera from people vaccinated with either of these vaccines also neutralise the UK B.1.1.7 isolate as well as the isolate from Wuhan. So, that’s good news. 

More importantly, we got data from the Johnson & Johnson (J&J) vaccine trial out of South Africa on Friday, 29 January. We were lucky. We didn’t know when we conducted the J&J trial that there would be marked viral strain differences between South Africa and the US. 

The J&J vaccine protected against hospitalisation and death in 88% of the enrollees in South Africa – that’s 88%! Zero deaths in the vaccine group; six in the placebo group. 

In fact, when I worked with the company to design the trial, the reason we went to South America and South Africa for an international trial was because J&J is a global company and they wanted a globally developed vaccine. 

My network was already working with them on their experimental HIV vaccines and we had great investigators in both South Africa and South America who were tackling the Covid-19 epidemic and wanted to help in developing a vaccine. 

We were conducting so many trials in the US that we felt we could distribute some of the work internationally and everyone would benefit. At the time, we didn’t realise how fortuitous this decision was. 

A month ago, after the South Africans noted that the B.1.351 variant was the main circulating strain in the country, we got nervous because South African scientists were reporting that the B.1.351 variant could not be neutralised by convalescent sera from persons infected with the earlier circulating strains of the virus in South Africa; this was confirmed by a number of US-based laboratories.

Fortunately, this anxiety was alleviated on the evening of 28 January with the announcement of the data from the trial. 

The J&J vaccine protected against hospitalisation and death in 88% of the enrollees in South Africa – that’s 88%! Zero deaths in the vaccine group; six in the placebo group. 

Overall, the vaccine was 57% effective against moderate and severe disease. 

The efficacy number in the US was 72%; in Brazil, 71%. So, yes, we do have an 18% to 20% difference in the effectiveness in the J&J vaccine. And I will add that the Novavax vaccine, which showed 90% effective in the UK, showed 55% protection in South Africa. So, here, too, a reduction in efficacy to the South African variant using our current vaccines.

But to put it in perspective: What’s more important – do we develop these vaccines to reduce the frequency and severity of us having sore throats and cough? Or do we develop these vaccines to prevent us from getting hospitalised, or put on oxygen, put on a ventilator, or dying? 

I think all of us would take a vaccine that prevented us from dying, even though it might still mean a mild case of Covid-19 with a sore throat and a headache and some body aches for a couple of days.

I think I’d take that deal. I could elaborate, but that’s enough for one message. 

In my next piece, I’ll talk more about the J&J vaccine and where it fits into the vaccine response in the US and globally. We need a bit more data to become public before we tackle this task. 

There are lots of opinions here and there’s nothing wrong with that. But it’s been a very good week. This past week has brought two new safe and effective vaccines – Novavax and J&J – into our world. That can be nothing but great news. 

As in all science, all good clinical trial outcomes lead to more good questions that we’ll need to solve to control this pandemic. DM/MC

Dr Larry Corey is the leader of the Covid-19 Prevention Network (CoVPN) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV Covid-19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at the University of Washington and a Professor in the Vaccine and Infectious Disease Division and past president and director of Fred Hutchinson Cancer Research Center.

Information pertaining to Covid-19, vaccines, how to control the spread of the virus and potential treatments is ever changing. Under the South African Disaster Management Act Regulation 11(5)(c) it is prohibited to publish information through any medium with the intention to deceive people on government measures to address Covid-19. We are therefore disabling the comment section on this article in order to protect both the commenting member and ourselves from potential liability. Should you have additional information that you think we should know, please email [email protected]

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"Information pertaining to Covid-19, vaccines, how to control the spread of the virus and potential treatments is ever-changing. Under the South African Disaster Management Act Regulation 11(5)(c) it is prohibited to publish information through any medium with the intention to deceive people on government measures to address COVID-19. We are therefore disabling the comment section on this article in order to protect both the commenting member and ourselves from potential liability. Should you have additional information that you think we should know, please email [email protected]"

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