Posts Tagged ‘H5N1’

And while they were arguing about killer H5N1…

8 February, 2012

…Elsevier’s Virology was calmly publishing another paper on a “mutant” H5N1….

The abstract:

Acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly α2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans. [my emphasis – Ed]

I have covered the use of glycan arrays to characterise influenza viruses’ binding specificity previously; I thought then, and do now, that it is a very cool technology – and one that has shown in this case that H5N1 variants can be selected from an originally “wild” population, that preferentially bind the human-type receptor.

And they did it like this:

To examine the functional evolution of H5 HA receptor specificity in the laboratory, we implemented an in vitro receptor-binding virus enrichment approach that recapitulates in vivo selection. Synthetic 6′-sialyl (N-acetyl-lactosamine) (6′ SLN) was used as the affinity ligand mimicking the human receptor to capture spontaneous viral receptor variants on the surface of magnetic beads. Starting with a pool of 108 EID50 of A/Vietnam/1203/2004 (VN04 virus), we performed four consecutive rounds of in vitro binding and elution followed by isolation of 150 individual virus clones by plaque purification and characterization by sequence analysis.

No “genetic engineering” here – or furore over “killer viruses escaping the lab!”  Possibly because (a) “mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets”, and (b) “a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets” [my emphasis].

Meaning they didn’t actually make anything that could immediately elicit such scare-mongering as the more notorious studies I and many others have reported on previously.

However, the grim NSABB folk were quick to decry the publication, saying “”I think it is fair to say that we would have liked to have seen it before it was published,” [Paul Keim, chairman of the National Science Advisory Board for Biosecurity], and the “…altered bird flu virus could mutate in dangerous ways if unleashed in nature”.

I am more worried, to be perfectly honest, over the dangerous ways the the wild type virus could mutate IN nature, given that mutants can be selected so apparently easily!

Protection against Killer Flu! No, not H5N1…

17 January, 2012

Depiction of virus mixing in a pig

In an issue of Virus Research devoted to commemorating the career of Brian Mahy, who retired recently from the CDC and now as Editor-in-Chief of Virus Research, there is a paper by Taubenberger and Kash on the 1918 H1N1 flu – wherein they say the following:

“In a recent set of experiments, it was shown that mice vaccinated with the monovalent 2009 pandemic H1N1 vaccine were completely protected in a lethal challenge model with the 1918 influenza virus…”

Because the modern pandemic “swine flu” H1N1 HA protein descends directly from the 1918 virus, but in pigs rather than in humans. Remember all the hype around THAT work – resurrecting the legendary Spanish Flu, and how it would kill us all? And here we already have a vaccine, that will completely protect us.

We have vaccine candidates against H5 as well. Time for a universal flu vaccination campaign and pre-emptive strike, people!

Killer Flu hype grinds on

16 January, 2012

The Independent today has a story entitled”Killer flu doctors: US censorship is a danger to science” – thanks, AJ Cann! – which details how the folk in the Netherlands who did the work do not think the USA should not be “…be allowed to dominate the debate over who controls sensitive scientific information that could be misused in biowarfare terrorism”.

Influenza A viruses mixing in susceptible hosts


Well, yes, join the club, guys!  The article is quite reasonable – apart from a couple of points, noted below – but it ends on a suitably alarmist note “…the chances of a laboratory strain of H5N1 escaping into the wild remain high if it is stored in conventional flu-virus labs”, and “Regulators should not be sitting idly by, while the threat of a man-made pandemic looms”.  Really?  The undoubtedly very small amount of mutated flu that exists, relative to any engineered bioweapon in US or Russian labs, represents a clear and present threat to world health?

What dismayed me most, however, was how horrifyingly uninformed most of the commenters are – about H5N1 in particular, and science and science funding in general….!  As I could not comment there – Disqus broke, apparently – I will do so here.

As for labelling the article “Killer Flu Doctors” – really!  A little sensationalism, anyone??  Concerning the comment “…the details could be misused by rogue states or by biowarfare terrorists with access to rudimentary scientific knowledge and fairly standard laboratory equipment”: as a practicing molecular virologist, I can tell you that you would need a lot more than “rudimentary scientific knowledge” – you’d need skill in molecular biology, and especially in reverse genetics of (-)strand RNA viruses, as well as more than “fairly standard equipment” to even BEGIN to hope to make anything like a “killer” H5N1 from published details.

Additionally, a H5 N1 flu virus that is  aerosol transmitted in ferrets – and how efficient was that, I ask? – may NOT be similarly transmissible or as easily (if it was easy) between humans.  I will point out that people thought the SARS CoV outbreak was the “Big One” flu pandemic – but although it was aerosol transmissible, it wasn’t nearly as efficiently transmitted as the common flu, so did not spread as fast.

Thus, most of what the doomsayers are predicting could be simply hype – meanwhile, in countries far away from the US which seeks to regulate such work, the virus is already endemic, and mutating freely – and it would be VERY useful indeed to know what to look for!

Influenza virus migrations – a lesson from 1961

13 January, 2012

Influenza A viruses carried by birds

I have been doing quite a lot of digging into virus history recently, and it was interesting to pick up – while checking on who had published what from our University on viruses – a paper from 1966 describing “The isolation and classification of Tern virus: Influenza Virus A/Tern/South Africa/1961″ by WB Becker of the Virus Research Unit here at UCT.  It is interesting because it was isolated from sick migratory Common Terns along the south coast of South Africa, which were infected as part of an “explosive epizootic” which resulted in many deaths.  It became more interesting when it was shown in 1967 to cause few or no symptoms in Swift Terns but was shed in large amounts, to be highly pathogenic in chickens, and was subsequently typed as H5N3.

The discussion of the original paper was not only highly prescient, but may be completely valid today: a significant quote follows.

The isolation of Tern virus raises interesting epidemiological possibilities. The outbreak in chickens in Scotland caused by Chicken/Scot. virus preceded the Tern epizootic by about 17 months and occurred during stormy weather which drove sea-birds a little inland to take shelter. Large numbers ofHerring Gulls (Larus argentatus) were at that time working thef arm at which the out break in chickens occurred in November 1959 (J. E. Wilson, personal communication). The chickens might have contracted the infection from sea-birds, a viewpoint possibly supported by the preceding mass mortality in Kittiwakes (Rissa tridactyla) and Fulmars (Fulmaris glacialis) from February to August 1959 (Joensen, 1959) off the coast of Britain and Scandinavia. Unfortunately the aetiology of the last-mentioned outbreak was not investigated, but it is tempting to think it was caused by the Tern virus which was isolated at Cape Town some 18 months later in 1961, from migrant European Common Terns.

One might postulate: that certain sea-birds suffer latent or sporadic infection with avian influenza; that epizootics may be precipitated in them by conditions of stress, e.g. poor feeding under unfavourable weather conditions such as pre- ceded the Tern epizootic; and that spread to other sea-birds or domestic poultry may occur. [my emphases – Ed]

The 1967 tern infection paper continues this theme:

The outbreak in chickens in Scotland in 1959 (Dr J. E. Wilson, personal communication) and the Tern epizootic in 1961 were caused by influenza A viruses with closely related strain specific antigens which were unrelated to those of any previously known influenza A viruses. Recently strains of influenza A related to the Tern and Scottish viruses were isolated from turkeys in Canada (Dr G.Lang, personal communication). This lends further support to the hypothesis that migrating sea-birds such as the Common Tern may transmit avian influenza A viruses to domestic poultry.

This was followed up more recently (2002) by a paper describing transmission of the tern virus to laughing gulls:

This investigation detailed the clinical disease, gross and histologic lesions, and distribution of viral antigen in juvenile laughing gulls (Larus atricilla) intranasally inoculated with either the A/tern/South Africa/61 (H5N3) (tern/SA) influenza virus or the A/chicken/Hong Kong/220/97 (H5N1) (chicken/HK) influenza virus, which are both highly pathogenic for chickens. Neither morbidity nor mortality was observed in gulls inoculated with either virus within the 14-day investigative period. Gross lesions resultant from infection with either virus were only mild…. Antibodies to influenza viruses …at 14 DPI were detected only in the two tern/SA-inoculated gulls and not in the two chicken/HK-inoculated gulls.

Their conclusions, too, were rather disturbing:

The positive isolation of the tern/SA and chicken/HK viruses from the OP and cloacal swabs suggests that, with adequate exposure, gulls could serve as hosts for these and possibly other HPAI viruses. Isolation of the A/gull/Germany/79 (H7N7) virus during a HPAI outbreak in Eastern Europe provides further evidence to support the potential for pelagic birds to serve as biological vectors for (HP)AI viruses (D. J. Alexander, pers. comm., originally referenced in 29). This is a significant finding in terms of the epidemiology of AI viruses, especially considering the fact that the chicken/HK virus was a zoonosis (26,27). Moreover, pelagic birds have been implicated as the source for other AI viruses that transmitted to and may have caused disease in mammals (8,13).

Everybody is obsessed with H5N1: maybe we should be a little more concerned with what may be raining down from above, as seabirds carry recombinant / reassortant viruses from areas of high H5N1 endemicity around the world.


Worst virus EVER!!

3 January, 2012

Sigh…looks like we’re still all going to die…Science’s comment section has the following article from November 23:

Scientists Brace for Media Storm Around Controversial Flu Studies

My comment to the article:

“”This work should never have been done,” says Richard Ebright.”

Really? We shouldn’t know just what makes H5N1 flu aerosol-transmissible in ferrets, and potentially also in humans? And more to the point, people in countries where the virus is now endemic, and busy evolving without the permission of the NSABB or any other agency, shouldn’t know what to look for?

I am also concerned over the scare factor that keeps getting invoked: the same thing was said about reviving the 1918 H1N1, and the same counter can be made.


H5N1: coming soon to a ferret near you?

20 December, 2011

From Nature News today:

“It is a nightmare scenario: a human pandemic caused by the accidental release of a man-made form of the lethal avian influenza virus H5N1.

Yet the risk is all too real. Since September, news has been circulating about two groups of scientists who have reportedly created mutant H5N1 variants that can be transmitted between ferrets merely breathing the same air, generally an indicator that the virus could also spread easily among humans.”

And yet…and yet…we won’t know, will we? Until and unless a human catches the ferret-bred virus, OR one develops all by itself out here in the world, that has the same mutations – which we won’t know about, unless we are told what those are.

Wednesday 21st December
And updating this story: the BBC has an interview with Anthony Fauci – formerly head of the US NIH – on what will be happening with the information.  The answer – it will be “redacted”, so the conclusions are published, but not the methods the groups used to produce their viruses.  Apparently the redacted details will be shared with national health authorities and “reputable” universities and institutes.

I would be very interested to see who makes those decisions, and who is considered ‘reputable” – our group, at the best university in Africa and 103rd best in the world by some rankings, are not even reputable enough to be able to order bluetongue virus genes from DNA synthesis companies, for example.

Watch this space….

Help! We’re all going to die! Or – are we??

5 December, 2011

My son has just alerted me to a news item from the Russia Today site, which reports the following dry little item:

“A virus with the potential to kill up to half the world’s population has been made in a lab. Now academics and bioterrorism experts are arguing over whether to publish the recipe, and whether the research should have been done in the first place.

The virus is an H5N1 bird flu strain which was genetically altered to become much more contagious. It was created by Ron Fouchier of the Erasmus Medical Centre in Rotterdam, the Netherlands, who first presented his work to the public at an influenza conference in Malta in September.”

Right – nothing to get upset about, then?  Or….

Some background: what researchers did was to passage – that is, repeatedly infect new animals with virus from another animal – H5N1 influenza virus from birds, in ferrets.

Why ferrets?  Well, it was discovered by accident some 70+ years ago, that human flu viruses are very infectious in ferrets, and the reaction of ferrets to some extent predicts what will happen in humans – although they tend to die rather often from lab infections.

The result of the passaging was that the H5N1 became aerosol-transmissible – in other words, via droplets produced by sneezing – which was a new property.  From the article:

“After 10 generations, the virus had mutated to become airborne, which means ferrets became ill from merely being near other diseased animals.

A genetic study showed that the new, dangerous strain had only five mutations compared to the original one, and all of them were earlier seen in the natural environment – just not all at once. Fouchier’s strain is as contagious as the human seasonal flu, which kills tens of thousands of people each year, but is likely to cause many more fatalities if released.

“I can’t think of another pathogenic organism that is as scary as this one,”
Paul Keim, a microbial geneticist who has worked on anthrax for many years, told Science Insider. “I don’t think anthrax is scary at all compared to this.””

Hence the rather alarming headline on RT – which was

“Man-made super flu could kill half humanity”

Nothing scare-mongering there, then!

Let us dissect this so called apocalypse bug, though.

“Fouchier’s strain is as contagious as the human seasonal flu, which kills tens of thousands of people each year, but is likely to cause many more fatalities if released.”

In ferrets.  No-one has shown that it causes disease in humans at all.  And there’s another problem: the article reports that:

“…the US National Science Advisory Board for Biosecurity (NSABB)…[has] a very difficult decision to make. Fouchier wants his study to be published. So does virologist Yoshihiro Kawaoka, who led similar research in collaboration with the University of Wisconsin, Madison, and the University of Tokyo, and reached comparable results. And it is up to NSABB to give them the green light.”

Pardon me for being confused, but…the NSABB is a US body, right?  And Ron Fouchier and Yoshihiro Kawaoka are Dutch and Japanese, respectively?

And pardon me again, but isn’t it a good idea to know which mutations would turn H5N1 into a ravening, destructive supervirus?  So we can look for it??  I would also think the cat is at least half out of the bag, because didn’t Ron Fouchier report the thing at a large conference already?

Letting paranoid folk in one country decide what is in the best interests of world science is NOT a good idea, in my opinion – but as has already been made abundantly clear, the developed world does not much care about our opinion.

So it goes.

H5N1 just rolls on, and on, and on….

31 August, 2011

It is a very interesting phenomenon, in the annals of influenza viruses, that avian H5N1 just keeps rolling on, and on, and on.  It was already the longest-lasting and most serious animal pandemic several years ago, and has caused immense economic damage.  And now – it seems to just get worse.  From Vaccine Nation:

H5N1 kills up to 60% of the people it infects. It has resurfaced in recent months, most notably in Cambodia where it has infected eight people this year, killing all of them.

Reuters report that the call came after the U.N. Food and Agriculture Organization (FAO) warned on Monday of a possible resurgence of bird flu and said a mutant strain of the H5N1 was spreading in Asia and beyond.

While scientists are uncertain if this new strain — called H5N1- — is more virulent in people, they said it was different enough from its predecessor to escape a human H5N1 vaccine that can tackle the parent strain.

recombining flu viruses

I have blogged a lot on influenza viruses and their vaccines – search this site via the facility to your right! – and I can only reiterate what I have said a few times already: we really, really need to have some way of rapidly responding to emerging flu viruses, including new and nasty variants of H5N1.

And a very good way of doing that, given a VERY low barrier to entry in terms of manufacturing cost compared to conventional vaccines, is via plants.  Several companies, including Medicago Inc, have embraced the use of transient expression in plants as a means of rapidly producing both seasonal and pandemic flu vaccines – and I will blog on that technology soon.

Meantime, let’s just hope the new technologies can keep pace with the evolution of the viruses they are aimed at combatting.  And that someone will actually fund us to do something for our country!


H5N1 flu: The End is still in sight

15 July, 2008

While the much-dreaded Big One – a major flu pandemic – still seems to be holding off, I am pleased to see that the latest edition of Nature has devoted an editorial and other commentary space to pandemic flu in general, and H5N1 flu in particular.

The Nature issue of 10th July 2008 – which has Ebola virus glycoprotein on the cover, about which, more later – has as its lead editorial title, “The long war against flu“.  The header goes on:

“That the H5N1 strain of bird flu has not yet caused a pandemic is no cause for complacency. Preparations for the inevitable must be redoubled to mitigate the potential devastation.”

My feelings entirely, and especially for the developing world – shared with you here and here, in MicrobiologyBytes, and here, in your own ViroBlogy.  It is all too easy to easy to fall into a state of complacency, or even H5N1 pandemic fatigue: however, this is really dangerous, especially for planners.  The editorial goes on:

“Five years after the deadly H5N1 avian influenza virus exploded into a global epidemic in birds, it has infected more than 300 people. Happily, it has not yet evolved into a strain that can transmit easily between humans — an event that would trigger a pandemic that could kill tens of millions. But as long as H5N1 continues to be present in animals, that risk persists. And with so many other flu strains out in the world, all constantly evolving, a flu pandemic is inevitable.”


“…improved control measures, especially for H5N1 itself, and public-health infrastructure are our frontline defences against a pandemic. Unfortunately, the overall control picture is bleak. Thailand, Vietnam and China have notched up successes in curbing outbreaks in birds, which is key to minimizing the chance that the virus can pass to humans. But South Korea had its worst outbreak ever in April, and the disease has become endemic in Indonesia, Bangladesh, Vietnam and Egypt. Eradication now seems impossible, and the task of containing the virus has become chronic and costly.”

Which sets the stage for Commentaries in the same issue: in “Ready for Avian Flu“, Tadataka Yamada et al. offer up “…a roadmap for heading off a global avian influenza catastrophe“.  They discuss how the WHO has made plans for stockpiling H5N1 vaccines, and that major vaccine manufacturers have offered to contribute – but also that the necessary allocation plan and ethics framework still need to be worked out.  They discuss how adjuvanting flu vaccines can reduce the dose by up to to four times, and how this together with dedicating the existing manufacturing framework – capable of some 500 million doses of trivalent vaccine a year  – to single-valency production, could allow some 6 billion doses a year to be produced.

Which, of course, would neatly cover the world’s population.  This sounds wonderful – but ignores the fact that H5N1 viruses are notoriously difficult to produce via conventional egg-based methods, which is what provides the bulk of the present manufacturing capacity….  Still, they also point out that adjuvanted, non-matched vaccines can still cross-protect against strains that have undergone seven or so years of genetic drift, meaning that stockpiled H5N1 vaccines could still be relevant in several years time.

They state the following:

“In the next 18 months we [Bill & Melinda Gates Foundation, the Pasteur Institute and the Wellcome Trust] will develop, maintain and disseminate a central inventory of funded research activities that are relevant to human influenza to ensure that stakeholders are well-informed. We will also coordinate roadmapping exercises to identify knowledge gaps. These will assist funders and researchers in establishing research-funding priorities, with specific focus on vaccines, drug therapies and epidemiology/population science (for example, diagnostics, surveillance, transmission and modelling). The Bill & Melinda Gates Foundation and the Wellcome Trust will collaborate to fund these activities.”

And how much developing country input will there be into this?  Distressingly little, probably, given the propensity of these funds to at best give money to developed country groups to work with developing country folk, but at least the roadmap addresses issues that are relevant to the whole world community.  Like intellectual property concerns, coordination of stockpiling and distribution, fair distribution, funding…and surveillance, the forgotten and possibly most important factor in determining if a flu outbreak is getting out of hand.  

Apropos of which, another commentary in the same issue – “The contents of the syringe“, by Steven Salzberg – notes that the influenza vaccine failed this northern hemisphere winter, and that future success relies on sharing data more widely and making the virus strain selection process more transparent.  Salzburg says:

“The WHO met on 11–13 February this year to decide on the strains to be included in the vaccine for the 2008–09 season. As usual, the meeting was closed to all but invited participants, who this year included members of the WHO influenza surveillance network, representatives of national drug regulatory agencies, and influenza vaccine manufacturers. The experts involved chose to replace the H3N2 strain with a more recent isolate, from 2007, which should be a better match to the circulating viruses next season. Neither the WHO nor the CDC publishes the evidence used to support their decision [my emphasis]. That evidence includes hemagglutinin inhibition tests of hundreds of isolates, genome sequences of some isolates and data on the ease with which the isolates can be grown in eggs.”

“The process of choosing flu-vaccine strains needs to be much more open. Other scientists, such as those in evolutionary biology with expertise in sequence analysis, could meaningfully contribute to the selection. At present, external scientists cannot review the data that went into the decision, nor can they suggest other types of data that might improve it.”

Whoops…so those who would safeguard us, feel no need to tell us what is going on??  Salzburg has some suggestions:

“The leaders of the influenza community, especially the WHO and the CDC, should create policies — for sharing data and isolates — that are more open, and should insist that their own scientists follow those policies. When these leading organizations set an example, the rest of the community will follow.”

“Of course, preparing vaccine in cell culture could reduce some of the pressures put on that dark room of vaccine predictors. The current system, in which most of the world’s vaccine supply is grown in chicken eggs, is an antiquated, inefficient method requiring six months or more to ramp up production, which in turn means that the vaccine strains must be chosen far in advance of each flu season. More crucially it sometimes prevents the use of the optimal strain, as it did in 2007. And, if the next pandemic is an avian-influenza strain such as H5N1, then it could easily sweep through the chicken farms that we rely on to produce eggs for vaccines. [me again]”

 He goes on to extol the benefits of sharing sequence information in particular, so as to enable rational, evidence-based choice of flu strains for vaccines – and the use of non-egg-based cell culture methods for vaccine production, and how these should allow far quicker development of flu vaccines.

All of this is very cogent and timeous.  However, it begs the question, previously raised in ViroBlogy, as to how production will be increased to take care of everyone who may be affected.

I still think plants are the answer…!  I note the plant-based flu vaccine group paper that I blogged on previously in this forum has a sequel: this is a better paper all around, and points up the need to explore this sort of production system for this kind of virus.

But I digress – so let me do so thoroughly.  The Nature issue also has a news item on the Eppendorf Song, a new piece of viral advertising with a boy band extolling the virtues of a multipettor.  Not a patch on the Biorad PCR Song, guys – but nice to see some popular culture making its way into science equipment advertising!

Bird Flu Vaccine Launched – But For Whom?

22 May, 2008

The online 20 May issue of Nature News trumpets the release and marketing of a new H5N1 bird flu vaccine: GlaxoSmithKline’s Prepandrix has just been approved by the European Commission. 

Published online 20 May 2008 | Nature | doi:10.1038/news.2008.844

Bird flu vaccine to hit the shelves

Europe approves pandemic vaccine; countries must decide own strategies.

Tony Scully

The European Commission has approved a new vaccine against the H5N1 bird flu virus — the first vaccine designed to ward off a future pandemic. But how the drug, called Prepandrix, will be deployed by national governments remains unclear.The vaccine, produced by the UK drug giant GlaxoSmithKline, is aimed at the H5N1 strain currently circulating in birds as epidemiologists think that this is the most likely strain to cause a human pandemic. H5N1, which originated in south-east Asia and is carried by migrating birds and domestic poultry, has caused 382 human cases and 241 deaths worldwide since 2003.

Prepandrix targets an antigen from an H5N1 strain called A/Vietnam/1194/04, which has been detected in birds in Asia, Europe and Africa. Clinical tests have shown that the vaccine is also effective against other closely related variants of H5N1, such as H5N2. The release of the vaccine is seen as a gamble that any future pandemic strain will closely resemble the Vietnamese version used to derive the vaccine.

The article goes on to describe how “The first orders for Prepandrix were placed last year by Finland and Switzerland, before it had been approved by the European Commission. In 2007, sales for Prepandrix totalled US$284 million worldwide….”

Yes.  Well.  Um.  Where is the pandemic going to hit first?  Finland?  Switzerland?  I doubt it.  How about Indonesia, Thailand, Vietnam, Turkey, Egypt…or, horror of horrors, India or China?  All the places which will need a LOT of doses, cheap.

Do they stand any chance of getting them?  Not unless they have preordered.  And not – in the case a pandemic strikes – unless they are willing to take military action to prise their stocks out of the hands of the governments in the developed countries where the vaccines are made.

A senior WHO official stated the case very succinctly, at the Virus Africa virology conference in Cape Town in November 2005: “You people in the developing countries will be on your own if the pandemic comes.  You need to make your own vaccine…”.

We wait in hope.