H7N9 Vaccine Realities

 

# 7073

 

While we are far from knowing how serious this H7N9 bird flu virus outbreak in China will ultimately become, there are people in the world who’s job it is to plan for a variety of `worst case’ pandemic scenarios.  

 

So it should come as little surprise that discussions over the possibility of developing an emergency pandemic vaccine for this virus are already underway around the globe.

 

The CDC has acknowledged their intention to pursue the development of a seed vaccine, as part of a series of `routine preparedness measures’ that are taken whenever a new virus threatens.

 

We’ve seen these sorts of precautionary steps before, with the H5N1, H3N2v and H7N9 viruses (see H3N2v Vaccine Trials & Bangladesh To Share H9N2 Bird Flu Virus).

 

This report from Reuters.

 

CDC to prepare bird flu vaccine just in case

By Reuters staff

The U.S. Centers for Disease Control and Prevention (CDC) said on Thursday it was monitoring a new strain of bird flu and has started work on a vaccine just in case it is needed.

 

So far, the strain known as avian influenza A (H7N9) is only in China and has not yet been found to be capable of being transmitted from person to person.

 

The strain has killed five people, and global health officials are debating whether to start mass-producing a vaccine.

 

(Continue . . . )

 

Via Japan’s NHK network, we get a report on an analysis released today by Japan’s National Institute of Infectious Diseases of the  H7N9 virus.

 

While we’ve yet to see direct evidence of human-to-human transmission  - this reassortant H7 virus is said likely able to replicate in the nose and upper airway - a trait that has long been suspected as needed to make avian flu viruses transmit more efficiently in humans.

 

The research team leader, Takato Odagiri, is calling for the development of a vaccine. Follow the link to read:

 

H7N9 flu virus differs from other viruses

 

Japanese researchers say the new strain of influenza virus spreading in China has different characteristics than other avian viruses. They are calling for the development of a new vaccine.

 

Experts at the National Institute of Infectious Diseases released their findings on Thursday. Their findings are based on gene sequences obtained from China of 2 Shanghai men who died from the infection and an Anhui Province woman in serious condition.

 

(Continue . . .)

 

 

And my thanks to Helen Branswell for tweeting this Reuters story earlier today on the complexities involved in switching from a seasonal flu vaccine run (already in progress) to a pandemic vaccine production schedule.

  

 

World experts debate case for new bird flu vaccine

Thu Apr 4, 2013 12:12pm EDT

• Experts in daily talks on risks posed by new China virus
• Researchers analysing samples to find vaccine candidate
• Decision to make vaccine depends on whether H7N9 spreads

By Ben Hirschler and Kate Kelland

LONDON, April 4 (Reuters) - Experts from around the world are in daily talks about the threat posed by a deadly new strain of bird flu in China, including discussions on if and when to start making a vaccine.

 

Any decision to mass-produce vaccines against H7N9 flu will not be taken lightly, since it will mean sacrificing production of seasonal shots. And scientists warn it will take months to get any finished bird flu vaccine to the market.

 

But the groundwork is being laid.

(Continue . . .)

 

We do have some recent experience with rolling out an emergency pandemic vaccine. 

 

Even though the first H1N1 vaccines came off the production line in the fall of 2009, it proved too little & too late to have much of an impact on the second pandemic wave. 

Estimates made In May of 2009 by Dr. Marie-Paule Kieny, director of the WHO's Initiative for Vaccine Research, (see CIDRAP Experts to discuss swine flu vaccine decision May 14) gave our global vaccine production capacity as:

 

. . . .  somewhere between 1 billion and 2 billion doses in a year, based on an estimated seasonal vaccine capacity of about 900 million doses. Current world population is more than 6 billion.

 

"Being conservative, we think there'll be at least between 1 and 2 billion doses," she said.

 

But at the end of the day, things did not go nearly as well as originally planned and the global production of vaccine fell far short of these estimates.

 

In fairness, the yield from the seed virus proved less than anticipated and the use of adjuvants – to reduce the amount of antigen needed per shot – was met with public resistance.

 

 

On the plus side (and this isn’t well appreciated), the vaccine produced came off the assembly line sooner than expected (albeit in small quantities), and has proven to be both safe and effective.

 

Which has to be seen as a considerable victory, even if the ultimate number of doses produced was disappointing.

 

In a world of 7 billion, the reality is that our ability to manufacture and (just as importantly) distribute a pandemic vaccine in  a short amount of time remains severely limited.

 

It is really a matter of unforgiving numbers.

 

Numbers that start with billions of people at risk from any novel pandemic virus, and end with the number of doses of vaccine that can be delivered in six to twelve months.

 

While improvements have been made in global vaccine manufacturing capacity since 2009, rolling out a pandemic vaccine is a huge undertaking.

 

It is likely that relatively few people could expect to see any novel pandemic vaccine in less than six months from the time production started.

 

And most of the world would probably still be waiting after a year.

 

Five  and a half years after she first wrote it, there is probably no better overview of the problems in the creation, production, and distribution of a pandemic vaccine than Maryn McKenna’s  award winning 7-part series the Pandemic Vaccine Puzzle which she penned in 2007 for CIDRAP.

 

Part 1: Flu research: a legacy of neglect
Part 2: Vaccine production capacity falls far short
Part 3: H5N1 poses major immunologic challenges
Part 4: The promise and problems of adjuvants
Part 5: What role for prepandemic vaccination?
Part 6: Looking to novel vaccine technologies
Part 7: Time for a vaccine 'Manhattan Project'?
Bibliography

Well worth revisiting.

ECDC Epidemiological Update On Novel Coronavirus – Feb 13th

Coronavirus – Credit CDC PHIL

 

# 6934

 

For the second time in three days events have prompted the ECDC to release a new epidemiological update on the novel coronavirus that – until today – we’ve only seen acquired in the Middle East.

 

Earlier today, in HPA Confirms Locally Acquired Coronavirus Infection In UK, we learned that a family member of a man who recently returned from the Middle East with the virus has now been diagnosed with same infection.

 

The ECDC released an update on Monday of this week (see ECDC Update On Novel Coronavirus) with a table of 10 confirmed cases.  Today they update that table, and state that in view of the latest  human-to-human transmission they will be updating their risk assessment.

 

Epidemiological update: Case of severe lower respiratory tract disease associated with a novel coronavirus

13 Feb 2013

ECDC

On 13 February 2013, the HPA announced that one family contact of the previously-confirmed case reported on 11 February was laboratory-confirmed to be infected with the novel coronavirus (NCoV). This second case from the same family was hospitalised on 9 February with a short history of respiratory symptoms. The patient has an existing medical condition that may make him more susceptible to respiratory infections. He does not have a recent travel history, and is currently receiving intensive care treatment.

 

The cases have been notified through the EU alerting system for communicable diseases.

 

This brings the total of laboratory-confirmed cases of severe pneumonia caused by the NCoV to eleven globally (see table below).

 

The information available suggests human-to-human transmission of the NCoV in this family cluster.

 

The HPA reports that surveillance of family, close contacts of the two patients and healthcare workers treating the two patients is ongoing, as per the UK National Guidelines. None are currently presenting with symptoms consistent with nCoV.

 

The HPA is also following-up regarding passengers who may have been exposed while flying with the case announced on 11 February 2013 and are in contact with the airline concerned.

 

In light of this human-to-human transmission of the NCoV within the family cluster, ECDC is now updating its risk assessment, previously published on 7 December 2012.

 

 

 

For earlier blogs on the emergence of the novel coronavirus you may wish to revisit:

 

WHO Update On Novel Coronavirus

mBio: Coronavirus Has An Affinity For Multiple Hosts

WHO: Background & Summary Of Coronavirus Cases

Branswell On Expanded Surveillance For The Coronavirus

EID Journal: EMC/2012–related Coronaviruses in Bats

 

Photo Credit NIAID

 

# 6864

 

Yesterday, in EID Journal: Ebola Virus Antibodies From Bats In Bangladesh, we looked at the possible carriage of the Ebola virus in Asian bats, and reviewed some of the history of emerging zoonotic diseases that can be carried by these winged mammals.

 

Today,we have another Chiropterist’s delight, an EID Journal dispatch that reports on the presence of betacoronaviruses – similar to the ones that infected a small number of people in the Middle East last year – among bats sampled in Ghana, and across four European nations.

 

First, a brief review of the outbreak of this novel coronavirus, which began in April of 2012.  This from the World Health Organization.

 

Background and summary of novel coronavirus infection – as of 21 December 2012

Over the past three months, WHO has received reports of nine cases of human infection with a novel coronavirus. Coronaviruses are a large family of viruses; different members of this family cause illness in humans and animals. In humans, these illnesses range from the common cold to infection with Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS CoV).

 

This summary provides the latest information on all reported cases and provides details of a WHO mission to Jordan, which has concluded since the last web update.

 

Thus far, the laboratory confirmed cases have been reported by Qatar (two cases), Saudi Arabia (five cases) and Jordan (two cases). All patients were severely ill, and five have died.

 

<SNIP>

 

WHO recognizes that the emergence of a new coronavirus capable of causing severe disease raises concerns because of experience with SARS. Although this novel coronavirus is distantly related to the SARS CoV, they are different. Based on current information, it does not appear to transmit easily or sustainably between people, unlike the SARS virus.

(Continue . . . )

 

 

While we’ve not seen any new reports of illness from this virus in several months, the memories of the SARS outbreak in 2002-2003 remain fresh. Although this new Coronavirus (dubbed Human Betacoronavirus EMC/2012) isn’t SARS, it does come from the same family.

 

Last September, in Coronavirus `Closely Related’ To HK Bat Strains, we looked at research from the University of Hong Kong that compared the genetic structure of this newly discovered coronavirus with other coronaviruses, and found it to be a 90% match to the HKU4 and HKU5 strains collected in the middle of the last decade in Hong Kong.

Since then we’ve seen additional evidence suggesting that bats are likely this virus’s natural reservoir in mBio: New Coronavirus Linked To Bats and mBio: Coronavirus Has An Affinity For Multiple Hosts.

 

But so far, the viruses found in bats have been similar, but not a really close match to the HCOV EMC/2012 virus.

 

In an EID Journal dispatch published today, we get word of the closest match to date between this mystery-shrouded emerging coronavirus, and viruses identified in bats.

 

First the link and abstract (or follow the link to read it in its entirety), then I’ll return with a summation.

 

Human Betacoronavirus 2c EMC/2012–related Viruses in Bats, Ghana and Europe

Augustina Annan, Heather J. Baldwin, Victor Max Corman, Stefan M. Klose, Michael Owusu, Evans Ewald Nkrumah, Ebenezer Kofi Badu, Priscilla Anti, Olivia Agbenyega, Benjamin Meyer, Samuel Oppong, Yaw Adu Sarkodie, Elisabeth K.V. Kalko, Peter H.C. Lina, Elena V. Godlevska, Chantal Reusken, Antje Seebens, Florian Gloza-Rausch, Peter Vallo, Marco Tschapka, Christian Drosten, and Jan Felix Drexler

Abstract

We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats.

 

The entire report is much longer, and quite detailed, but briefly:

 

Fecal specimens were collected from 14 bat species from 7 locations across Ghana and 5 areas in Germany, the Netherlands, Romania, and Ukraine, and analyzed for the presence of HCOV EMC/2012-like viruses using nested reverse transcription PCR (RT-PCR). 

 

Previously, 2c bat CoVs have only been detected in vespertilionid bats, but in Ghana they detected related viruses in Nycteris bats as well. While similar to the HCOV EMC/2012 virus, they were from a genetically distinct group. 

 

The authors write:

 

This novel Nycteris bat CoV differed from the 2c-prototype viruses HKU4 and HKU5 by 8.8%–9.6% and from EMC/2012 by 7.5% and thus constituted a novel RGU.

 

In 2008 a bat coronavirus was identified in the Netherlands called VM314 that partial sequencing has shown to be fairly closely related to HCOV EMC/2012.

 

In examining 272 P. pipistrellus, P. nathusii, and P. pygmaeus bats from the Netherlands, Romania, and Ukraine they found 14% carried coronaviruses that were closely related to VM314.

The authors write:

 

The VM314-associated Pipistrellus bat betacoronaviruses differed from EMC/2012 by 1.8%. The difference between EMC/2012 and HKU5 was 5.5%–5.9%.

 

In summary, HKU5, EMC/2012, and the VM314-associated clade form 1 RGU according to our classification system, and the VM314-Pipistrellus bat clade contains the closest relatives of EMC/2012.

 

HKU4 and the Nycteris CoV define 2 separate tentative species in close equidistant relationship.

 

After calling for surveillance and screening of bats in the Middle East where these scattered human infections have been documented, the authors conclude:

The genomic data suggest that EMC/2012, like hCoV-229E and SARS-CoV, might be another human CoV for which an animal reservoir of closely related viruses could exist in Old World insectivorous bats(4,9).

 

Whether cross-order (e.g., chiropteran, carnivore, primate) host switches, such as suspected for SARS-CoV, have occurred for 2c clade bat CoVs remains unknown.

 

However, we showed previously that CoVs are massively amplified in bat maternity colonies in temperate climates (13). This amplification also might apply to the Nycteris bat CoV because, as shown previously for vespertilionid bats from temperate climates (14), detection rates of CoV are significantly higher among juvenile and lactating Nycteris bats.

 

In light of the observed high virus concentrations, the use of water from bat caves and bat guano as fertilizer for farming and the hunting of bats as wild game throughout Africa (15) may facilitate host switching events.

 

To our knowledge, no CoV has been isolated directly from bats. Further studies should still include attempts to isolate full virus genomes and to identify virulence factors that might contribute to the high pathogenicity of EMC/2012 (7).

ECDC: Updated Novel Coronavirus Risk Assessment

Photo Credit NIAID

 

# 6770

 

Although we’ve no fresh reports of infection by the novel coronavirus which appeared in the Middle East last April, and has been confirmed in 9 patients (see WHO: Background & Summary Of Coronavirus Cases), health officials around the globe continue to assess the situation and make provisions to detect and contain the virus.

 

A week ago the World Health Organization  released new Interim surveillance recommendations and an updated Coronavirus FAQ (see WHO Coronavirus Updates).

 

Today, in the wake of the announcement of two cases from Jordan last spring, the ECDC updates their Coronavirus Risk Assessment, previously updated on November 26th.

 

Novel coronavirus: ECDC updates its risk assessment

10 Dec 2012

 

ECDC has published another update of its risk assessment on the novel coronavirus. Two cases in Jordan have retrospectively been confirmed. These additional cases have increased the geographical area in which transmission of the virus has occurred. The two fatal cases were part of a cluster of 11 patients with respiratory symptoms linked to a hospital. The limited information available about this outbreak does not allow for an assessment of whether human-to-human transmission has occurred or indeed whether the cases in this cluster had the same cause.

 

The ECDC risk assessment highlights that healthcare workers should be alerted to the possibility of attending to patients who meet specific characteristics which would require an investigation according to the WHO case definition. The new WHO recommendations favour the investigation of patients returning from the Arabian Peninsula or its neighbouring countries, but do not exclude the testing of patients with unexplained pneumonia in the absence of such travel.

 

A specific serological test and seroepidemiological studies are needed to investigate the occurrence of mild and asymptomatic infections. The diagnostic capacity for novel coronavirus is adequate in the EU. This is confirmed by a newly published article in Eurosurveillance on the results of a survey undertaken by ECDC and WHO. The virus genome is in the public domain and mechanisms for sharing samples and diagnostic methods between countries and laboratories are in place.

 

As of 4 December 2012, a total of nine laboratory-confirmed cases of severe pneumonia caused by the novel coronavirus have been reported to WHO. Five of the nine cases were fatal. Onset of disease was from April to October 2012 and all cases were resident in Saudi Arabia, Qatar or Jordan during the presumed 10 days incubation period.

 

ECDC endorses the WHO travel advice and does not advise any travel or trade restrictions for Saudi Arabia or Qatar.

 

The entire Risk Assessment may be downloaded here.

 

This document’s main conclusions and recommendations reads:

 

• As of 4 December 2012, nine laboratory-confirmed cases of severe pneumonia caused by the novel coronavirus have been reported to WHO. Five of the nine cases were fatal. Onset of disease was from April to October 2012; all cases were resident in Saudi Arabia, Qatar or Jordan during the presumed 10 days incubation period.
• Two retrospectively tested and confirmed cases in Jordan in April 2012 have increased the geographical area in which transmission has occurred. The two fatal cases were part of a cluster of 11 patients with respiratory symptoms linked to a hospital, but the limited information available about this outbreak does not allow for an assessment of whether any human-to-human transmission occurred or whether the cases in this cluster had the same cause.
• Healthcare workers should be alerted to the possibility of attending to patients who meet the WHO case definition. Such cases should be investigated rapidly and managed according to WHO recommendations or national guidance documents.
• The new WHO recommendations for the investigation of patients favour the investigation of patients returning from the Arabian Peninsula or its neighbouring countries, but do not exclude the testing of patients with unexplained pneumonia in the absence such travel.
• Healthcare workers caring for patients under investigation should exercise stringent infection control measures as indicated by national or international guidance. Similarly, health professionals engaged in the medical evacuation of patients presenting with acute respiratory distress syndrome (ARDS) should be particularly vigilant, especially if patients originate from the Arabian Peninsula or its neighbouring countries.
• Testing for the novel coronaviruses should be considered in patients undergoing medical evacuation for ARDS prior to their transfer out of the Arabian Peninsula or its neighbouring countries. All public and private hospitals and private healthcare facilities should test patients on admission for the novel coronaviruses if they present with ARDS and have been medically evacuated from the Arabian Peninsula or its neighbouring countries. Referring providers should inform the recipient hospital if testing for novel coronavirus has been performed.
• Healthcare workers caring for confirmed cases should be monitored for early symptoms of infection. This includes healthcare workers who provided direct clinical or personal care, or performed examination of the cases while they were symptomatic. Close contacts of confirmed cases must be monitored for symptoms as well.
• Any probable or confirmed case diagnosed in the EU/EEA should be reported to national authorities through the Early Warning and Response System (EWRS) and to WHO under the International Health Regulations (2005). Reporting through EWRS allows for an automatic IHR notification and avoids double reporting.
• Patients still under investigation do not need to be reported internationally before confirmation. However, notification at state and national levels needs to follow national legislation or guidance to allow the implementation of infection control measures, initiation of outbreak investigation, and epidemiological monitoring.
• A specific serological test and seroepidemiological studies are needed to investigate the occurrence of mild and asymptomatic infections.
• ECDC endorses WHO's travel advice and does not advise any travel or trade restrictions for Saudi Arabia or Qatar.
• WHO and ECDC re-emphasise the importance of timely and thorough investigations; this includes the reporting of any clusters of severe acute respiratory infections in the community or in healthcare workers, regardless of where in the world they occur.