Monday, July 20, 2020

`Forward Looking' & `Aspirational' Vaccine Press Releases


As a decidedly pro-vaccine blogger (I get the flu shot every year) - and one who views a vaccine as an important tool in battling COVID-19 - I'm in the uncomfortable position of being skeptical of the claims being bandied about by governments and pharmaceutical companies on the timeline to develop and deploy (in quantity) a safe and effective SARS-CoV-2 vaccine. 

I'd like to be proven wrong, of course. We desperately need a vaccine.  And I'm hopeful that eventually we'll get one. 
But vaccine creation and manufacturing is never easy, and problems can even crop up when making relatively simple influenza vaccines, something we've been doing since the 1940s.  

Last year, the world struggled to produce and distribute sufficient quantities of a seasonal flu vaccine (see NHS Update: More Global Flu Vaccine Delays), and in 2019's Manufacturing Pandemic Flu Vaccines: Easier Said Than Done, we looked at the long history of failed attempts to produce pandemic flu vaccines in quantity and in a timely manner

Despite past performances, governments, research centers, and pharmaceutical companies continue to accentuate only the positive, using `forward looking' statements and `aspirational' language to imply that a COVID-19 vaccine is just around the corner. 
Today the UK government published a press release on their purchase of 90 million doses of (3 different) experimental COVID-19 vaccines, which they hope will protect millions of Britons in the months ahead.  

A worthy goal, certainly - but these are all unproven candidate vaccines - and success is far from assured.  While carefully worded so that no direct promises are made, you won't find any caveats or cautionary statements either. 

Published 20 July 2020

From:Department for Business, Energy & Industrial Strategy, Department of Health and Social Care, The Rt Hon Matt Hancock MP, and The Rt Hon Alok Sharma MP
  • The UK government has secured early access to 90 million vaccine doses from the BioNTech/Pfizer alliance and Valneva with more in the pipeline as part of its strategy to build a portfolio of promising new vaccines to protect the UK from COVID-19
  • In addition, treatments containing COVID-19-neutralising antibodies have been secured from AstraZeneca to protect those who cannot receive vaccines
  • UK public encouraged to sign up to a new NHS website to make it quicker and easier for potential volunteers to join vital studies that could help save lives – the aim is to get 500,000 people signed up by October
Millions of people could be vaccinated against coronavirus as the UK secures early access to 90 million doses of promising COVID-19 vaccine candidates.
Announced by Business Secretary Alok Sharma today (Monday 20 July), the government has agreed significant partnerships with leading pharmaceutical and vaccine companies BioNTech/Pfizer and Valneva that are developing innovative new vaccines to protect people against coronavirus. The government has also secured access to treatments containing COVID-19-neutralising antibodies from AstraZeneca to protect those who cannot receive vaccines such as cancer and immunocompromised patients.

As a result of these partnerships, England, Scotland, Wales and Northern Ireland could have access to enough doses to vaccinate and protect priority groups identified, such as frontline health and social care workers and those at increased health risk.

With today’s announcement, the government has now secured access to 3 different types of COVID-19 vaccines that are being developed here and around the world, giving the UK the most likely chance of getting access to a safe and effective vaccine at the quickest speed.

The government has also today launched the NHS COVID-19 vaccine research registry. This new website will enable people in the UK to play their part by volunteering for future vaccine studies.

The new online service will allow members of the public to register their interest and be contacted to participate in clinical studies. To enable large-scale vaccine studies to take place across the UK, the aim is to get 500,000 people signed up by October, which is considered vital in the fight against coronavirus.

Clinical studies with hundreds of thousands of volunteers will help scientists and researchers better understand the effectiveness of each vaccine candidate and will considerably speed up efforts to discover a safe and workable vaccine.

The government is also working with ZOE, the health science company using data driven research and behind the popular symptom study app and site, to look at collaborating around vaccine studies and to help their volunteers hear about how to sign up to the NHS registry.
          (Continue . . . )

While this may not be the most blatant example of vaccine hype since SARS-CoV-2 emerged, it is certainly the most recent.

Obviously, governments want the public to believe that they are doing everything they can to bring this pandemic to an end, and hope is important for public morale going into an uncertain fall and winter.

But in a pandemic, I would submit it is better to under-promise and then over-deliver.  Particularly given our track record on coronavirus vaccine research.

Despite 17 years of trying, there is still no commercially available SARS vaccine, although not for a lack of trying.  In 2012, a PLoS One research article found that mice vaccinated with four different experimental SARS candidate vaccines developed the expected antibodies, but experienced lung damage when challenged with the virus.
Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus
Chien-Te Tseng, Elena Sbrana, Naoko Iwata-Yoshikawa, Patrick C. Newman, Tania Garron, Robert L. Atmar, Clarence J. Peters, Robert B. Couch

These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.
And eight years after MERS emerged in the Middle East a vaccine remains elusive (see Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism) for both camels and humans. 

Complicating matters, we've seen increasing research suggesting that natural infection with SARS-CoV-2 may provide only limited, and relatively short-term, antibody responses - which if confirmed to be true - could have serious implications for vaccine efficacy and the goal of achieving herd immunity. 

But let's assume that one or more safe and effective vaccine candidates can be developed, and that they provide at least a year's worth of reasonable (75%) protection against COVID-19.  

The task of manufacturing billions of doses and vaccinating billions of people represents a public health logistical challenge that far exceeds anything that's been done in the past.  
Will it take one dose, or two?  How far apart?   Will it require yearly (or occasional) booster shots?  How much public resistance will there be to any new, fast-tracked vaccine?   
During the 2009 pandemic, there were optimistic estimates that nearly 5 billion doses of the H1N1 vaccine could be produced in the first 12 months (see Recommendations of the Strategic Advisory Group of Experts (SAGE) on Influenza A (H1N1) vaccines.)

In the end those manufacturing goals fell short by 75% (see 2010's ECDC: Global Vaccine Goals And Realities), as 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.


I'm optimistic enough to believe that hundreds of millions of people - mostly in the developed world - will be offered a COVID-19 vaccine in 2021. How protective that will be, and for how long, remain open questions.  And we may not know those answers for another year or two. 

But even if a record two billion doses can be manufactured and administered in 2021 - assuming it takes two shots to convey immunity - only about 1 in 8 people on the planet could be immunized.
Double that output to 4 billion doses, and you are still only a little over 25% global coverage. And those are optimistic scenarios, where nearly everything will have to go right. 

While I would love to buy into the `happy talk' that we'll have one or more approved vaccines in the spring of 2021- and that within a few months COVID-19 will be rendered little more than a bad memory - the math and past performance argue against it. 

An effective vaccine will certainly help. It would undoubtedly save lives and help protect essential workers. It is a laudable goal, and I'm certainly not lobbying against it. 

But even with a vaccine - unless the virus somehow attenuates on its own, or we gain a lot of durable herd immunity from natural infection - COVID-19 is unlikely to be vanquished anytime soon.