Posts Tagged ‘Vaccine development’

COVID-19 Update And Promising Vaccine Reports

Monday, August 10th, 2020

An alarming and disquieting milestone

Yesterday, we passed the five million mark. Five million confirmed cases of COVID-19 in America since January. To put this in a better perspective consider this: If you took every one of those five-million people and stood them shoulder to shoulder, the line would extend from Canada to the Mexican border. About 2,200 miles.

As for deaths, we have reached 163,000, and still rising with no end in sight. That number is more than three times the number of American soldiers who died in World War 1. More than three times the number of American soldiers killed during the 16-year Vietnam War.

This continuing death spiral is happening as Congress and the Administration are, as legendary Boston sportscaster Johnny Most used to say, “fiddling and diddling.” And all this fiddling and diddling is going on while millions of our fellow citizens watch their livelihoods and their dreams of a better life for them and their children dissolve into thin air.

We deserve better than this. Fiddling and diddling with a human tragedy of this magnitude is an obscene abomination.

Vaccine update

In the pre-clinical biotech world, we call them non-human primates. To everyone else, they’re monkeys, usually rhesus monkeys.

We have reported, and I’m sure you’re aware, that a number of companies have entered Phase 3 clinical trials testing their vaccines on thousands of people. Until COVID-19, that always followed years of pre-clinical work that usually began with mice. But because regulators have compressed and redesigned the vaccine development process, companies and institutions are running their pre-clinical and clinical trials simultaneously, in parallel.

Now, four groups have reported promising results with non-human primates, those rhesus monkeys. All of the approaches are different, but they settle into two methodologies:

  • Attacking SARS-CoV-2, the virus that causes COVID-19, through Messenger RNA.
  • Using a replication-deficient chimpanzee adenovirus to deliver a SARS-CoV-2 protein to induce a protective immune response.

You don’t really need to understand the science. What is important to know is all four groups reported that their vaccines have shown promising results in monkeys. The critical thing here is this: Three or four weeks after vaccinating the monkeys, each of the groups put SARS-CoV-2 into the monkeys’ noses. Each of the vaccines offered protection for the monkeys. Three of the four groups gave the vaccine in two shots, a prime followed weeks later by a booster.

The team of Oxford University and AstraZenica injected with one shot. Their results presented some concerns. While their vaccine prevented the monkeys from developing pneumonia, it did not clear the virus, indicating the vaccinated monkeys remained infected and able to spread the disease. It should be noted that the scientists infected the monkeys with ten times the viral load that a person would experience. Still, the group said protection might have been significantly enhanced had they given two shots.

These monkey trials are tremendously important, because scientists can give the monkeys their vaccine and then infect them with SARS-Cov-2, something they cannot do with their human volunteers in their Phase 3 trials.

The four groups are:

  • Moderna, working with the Swiss company Lonza, New Jersey-based Catalent and the National Institutes of Health. Its vaccine, mRNA-1273, contains snippets of viral mRNA, a molecule with instructions for making proteins. Moderna packs the mRNA inside a slippery pod made of lipids, so it can slide easily into the cells.
  • Oxford University’s Jenner Institute, working with AstraZenica. Its vaccine, ChAdOx1, uses a replication-deficient chimpanzee adenovirus to deliver a SARS-CoV-2 protein to induce a protective immune response. Their approach has been successful before as the first Ebola vaccine.
  • Pfizer, working with BioNTech, a German biotechnology company. Their vaccine, BNT162b2, also takes the mRNA route encoding an optimized version of the whole spike protein, which we wrote about here.
  • Johnson & Johnson, working with Beth Israel Deaconess Medical Center in Boston. Its vaccine candidate, Ad26.COV2.S, delivers the SARS-CoV-2 spike protein into cells using an inactivated common cold virus as the delivery vehicle. J & J gave a single shot of Ad26.COV2.S, and that provided significant immunity to COVID-19. But previous J & J studies showed giving a second booster shot raised the antibody response by tenfold in both animals and people.

All of this is promising, indeed. It is evidence we should be optimistic that we’ll have one or more effective vaccines by early 2021. However, it is worth noting that the road to a successful vaccine is littered with the decaying carcasses of failures.

 

 

Why Dr. Fauci Is “Cautiously Optimistic”

Monday, August 3rd, 2020

As I’ve previously written, until now, vaccines have taken years to develop. The fastest until now? The Mumps vaccine, developed and approved in four years (1963 – 1967) by Maurice Hilleman.

In recent times we have the Ebola vaccine, approved in the U.S. in 2019. Scientists from around the world had tried to develop a vaccine for this deadly disease since the mid-1990s, but funding and, let’s face it, lack of interest in an African disease, continually stalled the work. But a large outbreak in the Democratic Republic of Congo in 2014 reignited Pharma’s interest, and last December the FDA approved Merck’s Ervebo vaccine. It took five years.

Now we have COVID-19, the disease caused by  SARS-CoV-2 (the scientific name of the new coronavirus), and immunologist Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases since 1984, is “cautiously optimistic” we’ll have a vaccine by the end of the year. This means we could have needles going into arms in less than a year since the first case was reported. How is that so?

Although Donald Trump would probably swallow his smart phone rather than acknowledge this, we owe a debt of gratitude to the Chinese for the quick start. In early January, before the disease even had a name, a team of Chinese scientists uploaded its genetic sequence to a public site. This kicked off the gold rush-like vaccine hunt. Here are some facts that contribute to the light-speed development:

  • The disease is a coronavirus. Scientists have been trying to develop vaccines for this family of diseases for decades. Coronaviruses are diseases that can leap from animals to humans, and much work had already been done. Vaccine projects currently underway were simply redirected to SARS-CoV-2.
  • Many of the vaccine teams now attacking SARS-CoV-2 had worked on the SARS virus, which in 2003 killed 800 people, and the MERS virus, which has killed 2,500 people since 2012. They were deep into coronaviruses.
  • The earlier projects had identified a part of coronaviruses called the spike protein as a potential target for a vaccine. In particular, the work on SARS had suggested strongly that the spike protein was the key. Moreover, that work had already identified the difficulties inherent in attacking the spike protein.
  • Most people recover from COVID-19. That indicates a conquering immune response that a vaccine can be targeted to induce in people.
  • The spike protein, which gives SARS-CoV-2 the crown-like appearance that’s characteristic of coronaviruses, attaches to receptors on people’s cells, allowing the virus to enter and replicate. By blocking spike proteins, then, vaccines may prevent infection.
  • Money is no object. Because COVID-19 is the biggest health crisis the world has faced in more than 100 years, governments are shoveling unheard of amounts of cash into vaccine development. If vaccine developers don’t have to worry about funding their work, they can try anything and everything without worry. And, most important, the traditional steps taken in vaccine development can be shortened and compressed, which is exactly what’s happening.
  • Government regulators learned a lot from Ebola. During the development of Ervebo, they adopted a new dexterity in streamlining decisions and a nimbleness in communication. That has continued over to COVID-19. Case in point: the FDA has let developers know that vaccines need to prevent infections or reduce the severity of Covid-19 in 50% of recipients to be approved.

Here is where we are now in vaccine development according to the New York Times Coronavirus Vaccine Tracker:

If you’re wondering about that one “Approval” on the far right, that is a vaccine developed by the Chinese company CanSino Biologics. Hong Kong-listed CanSino Biologics said in a filing to the stock exchange that data from clinical trials showed the Chinese military vaccine had a “good safety profile” and potential to prevent disease caused by the novel coronavirus. Consequently, on 25 June, China’s Central Military Commission approved the use of the vaccine for one year. The rest of the world has no idea of whether this vaccine works. One wonders what the soldiers in the Chinese Armed Forces who are being injected with it think of it.

If history is any predictor of the future, most of the vaccines currently under development will fail. However, the sheer size of the effort, as well as the mountains of work already done on SARS and MERS, suggest that Dr. Fauci’s cautious optimism may, indeed, be well founded.