“Constantly mutating variants is not something we expect with monkeypox”

24 May 2022

LMU virologist and vaccine researcher Gerd Sutter considers the probability of a monkeypox epidemic in Europe to be low – and sees numerous differences to the COVID-19 pandemic.

Prof. Gerd Sutter

Professor Gerd Sutter with teammates in the lab. | © LMU

Veterinarian Prof. Gerd Sutter Gerd Sutter holds the Chair of Virology in the Faculty of Veterinary Medicine at LMU. He carries out research into new vaccines and the global spread of previously unknown pathogens – and is considered one of the foremost pox virologists in Germany.

Professor Sutter, a new virus that leaps from an animal to humans, the first cases in Europe – Are we at the beginning of a monkeypox epidemic?

Gerd Sutter: No, I think the probability of a larger epidemic in Germany or Europe is low. The gradual process whereby the monkeypox virus is imported to Europe by travelers from Africa has been underway for years, and at the same time there has been an equally gradual outbreak in Nigeria. In isolated cases over the past few years, travelers have already carried the pathogen to the United States, Israel, Singapore, and Europe – in the latter case, primarily to the United Kingdom. What is completely new, by contrast, is that there is now a certain spread in Europe – and of course we have to keep an eye on that.

What are the differences to the Sars-CoV-2 pandemic?

There are fundamental differences to the coronavirus pandemic. Back then, it was a completely new pathogen and nothing was known about its biology. By contrast, we already know much more about the monkeypox virus – and have done for years. Monkeypox viruses belong to the Orthopoxvirus genus, of which we know that they can infect various hosts.

We also know that transmission takes place via direct contact and especially through highly infectious lesions. Transmission via droplets or aerosols plays an extremely minor role. Monkeypox transmissions are therefore relatively inefficient compared to infections with COVID-19 or influenza viruses and usually lead to short infection chains, when there are adequate measures for diagnosis and contact tracing in place.

In addition, there are established detection procedures for the virus. Verifying monkeypox viruses is quite straightforward for specialist virological facilities in Germany.

And there are vaccines and even a licensed drug.

Moreover, the virus is of a totally different type. Monkeypox is a DNA virus and its genetic stability is very different to that of RNA types such as coronaviruses or influenza viruses. Constantly mutating new variants, as we saw with SARS-Cov2 – this is not something we would expect with monkeypox and its generally very stable genome. In fact, the extremely subtle genetic changes could actually help us track transmission paths of the virus through Europe.

Main infectivity is located in the skin lesions

How can we protect ourselves against transmission?

For the most part, zoonotic infections with monkeypox in Africa take place through direct contact with wild animals – while hunting or preparing bushmeat. Transmissions from human to human are possible, but they generally require direct contact with infected persons.

The main site of infectiousness is in skin lesions, which develop after the first more general symptoms such as headache, muscular pains, and fever. Inside the fluid of these blisters and the scabs that subsequently form, the virus is present in huge quantities. Patients are generally no longer infectious once these scabs have fallen off and the blisters have healed.

What needs to happen to curtail the spread of monkeypox, even if its dynamics are not comparable with SARS-Cov2?

Naturally, the authorities – and I have the impression that they are already doing this well –have to trace contacts and introduce appropriate hygiene and, if necessary, quarantine measures. Recommending that contacts be vaccinated is also an option. But we will certainly not need to lay in any great store of vaccines.

Smallpox virus vaccines

Prof. Gerd Sutter

Professor Gerd Sutter, Chair of Virology at the LMU Faculty of Veterinary Medicine | © LMU

You yourself research and develop new vaccines, including against poxviruses. How effective are existing vaccines?

Modern pox vaccines, which are approved in Europe, Canada, and the United States, are based on the safety-tested Modified Vaccinia Ankara (MVA) virus, which cannot reproduce in mammals and which I myself have been working on since my doctoral thesis. It is a classic vaccination virus, which induces effective humoral immune responses – that is to say, antibodies – and at the same time cellular responses – that is to say, T-cells.

In the prevention of orthopox-virus-specific diseases, cellular immunity plays a particularly important role. With its clinically proven safety and effectiveness, the MVA is used to induce protective virus-specific T-cell responses. In my current research, incidentally, we are using the MVA to develop broadly effective vaccines against other newly emerging viral diseases. Here, the orthopox virus functions as a sort of vector that gives a piggyback ride, so to speak, to the gene sequences for vaccine antigens of other pathogens – such as MERS or COVID-19 – and smuggles them in, as part of the MVA genome.

Is the classic smallpox vaccination – from which older generations still bear a scar on their arms – effective in any way against monkeypox?

Partial protection is certainly to be expected. We know from individual observations that even decades after this mass immunization program by the WHO against smallpox, a memory immune response is still present. There is clear data that precisely the cellular, the T-cell immunity can still be verified for the specific virus – even when the antibody response in the serum has already disappeared. That being said, during the vaccination campaign against smallpox, nursing and vaccination staff received a booster vaccine every three years. It should be noted in this regard, however that smallpox was based on a different virus, one that is much more contagious and fulminant in its spread than monkepox.

Drug prevents shedding of new viruses from infected cells

How effective is the drug Tecovirimat, which is licensed here, against monkeypox?

This so-called small-molecules drug attacks precisely one protein of orthopox viruses in a highly specific manner, preventing the discharge of new viruses from infected cells. As such, it is very effective while also achieving good tolerance. We know this from initial clinical case reports – even if of course there have not yet been many of them. The approval of Tecovirimat was based on very many pre-clinical trials in a wide variety of animal models.

Why new viral infections are accumulating

SARS, bird flu, swine flu, MERS, Ebola, Zika, COVID-19, and now monkeypox – Are we experiencing a proliferation and acceleration of new diseases and of zoonoses in particular? Or is that just our subjective impression in the information age?

No, it is actually the case and also what virologists are seeing. We have been observing this development for 20 years now, starting in 1999 with the sudden conquest of North America by the West Nile fever: airplane, mosquito, arrival in New York – that was all it took for the virus to spread throughout the North American continent within just a few years.

Various factors play a role in the proliferation of new viral infections. Firstly, the growing global population means that people are constantly being pushed into regions where nobody lived before. Accordingly, human hosts are suddenly accessible to viruses with which people had never previously had any contact.

Diet also plays a role. For years, virologists have been observing these markets in China where new influenza viruses and indeed coronaviruses are demonstrably being transmitted from animals to humans.

And of course there is the increase in trade and travel on a globalized scale over the past few decades – which enables a new pathogen to hitch a ride with an airline passenger and get from Malaysia to Frankfurt in under two days. The rapidity of spread has dramatically increased.

Another factor is climate change. As a result of changes in temperature, viral vectors such as mosquitoes and ticks are penetrating into new territories.

Being prepared for new pandemics

After our experience with COVID-19, are medicine and society better equipped to prevent new pandemics?

For all the pain and misery that the COVID-19 pandemic visited upon us, one useful thing it has done is to create a global awareness that such events can actually happen – and that we must prepare for them. This includes ensuring that health systems are supplied with PPE and armed with effective containment strategies, but also that research thinks ahead regarding which pathogens could become dangerous and which vaccines could be needed.

Furthermore, it would certainly be wise to keep suitable production facilities ready for manufacturing drugs and vaccines – including factories here in Europe. I myself am involved in the Coalition for Epidemic Preparedness Innovation. Initiated and supervised by the WHO, this is a worldwide public-private partnership of companies and important research institutes. It monitors certain “most-wanted” viruses, of which it is thought that they could become dangerous under certain circumstances, such as the Crimean-Congo fever or the MERS coronavirus. The monkeypox virus, even if it seems threatening to the general public at the moment, is not on the most-wanted list.

Prof. Gerd Sutter is Chair of Virology at the Institute of Infectious Diseases and Zoonoses at LMU. He studied veterinary medicine at LMU, where he also completed his doctorate. As a postdoctoral researcher, he went to the National Institutes of Health, Bethesda, Maryland, USA, before completing his postdoctoral thesis in virology at LMU. After spells working at the Institute of Molecular Virology at the Helmholtz-Zentrum München and heading up the Department of Virology at the Paul-Ehrlich-Institut in Langen, he returned to his alma mater in 2009.

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