Posts Tagged ‘Vaccine development’

Now There Are Two, And Other Thoughts

Monday, November 16th, 2020

The Moderna Vaccine

Moderna’s announcement today that its vaccine candidate, mRNA-1273, is more than 94.5% effective in early trial results is wonderful news. Pfizer’s similar announcement from last week about its vaccine, BNT162b2, (also mRNA-based) gives us great hope that by mid-2021 the U.S. may have vaccinated most of the country’s population.

One advantage Moderna has over Pfizer is that its vaccine does not require “ultra cold storage,” as in minus 103 degrees Fahrenheit. As we wrote here, Pfizer says it has developed specially designed, temperature-controlled shipping packages, using dry ice, to keep its vials at roughly minus 103 below Fahrenheit for up to 10 days. But what happens if the doses are not used in ten days? This is one of the many things that is concerning governors and health care experts who are wrestling with the logistics of large-scale vaccinations.

We won’t know if Pfizer’s and Moderna”s vaccines can really do what it seems they might be able to do until the final results of their trials are known, but there is one thing we won’t know even then: How long will they protect us from the Coronavirus? Although both companies will follow all test subjects for a couple of years, if they each file quickly for and receive Emergency Use Authorization, which is all but guaranteed, they will go to market with about four months of data.

Will this lack of certainty about long-term protection cause people to forego vaccination? Personally, I don’t think so. But there is another possibility.

As we have seen for many months, despite the lack of competent leadership from 1600 Pennsylvania avenue, there are significant segments of the population taking the virus more seriously than others: seniors, those who are health-compromised, and myriad others who have paid attention to the science. It is conceivable these groups will take the vaccine, but refuse to return to any semblance of pre-pandemic life until long-term efficacy is known, and that won’t happen until well into 2022. If this happens, it is likely that masks, remote work, telehealth, and a host of other accommodations we’ve made due to the pandemic are here for quite some time longer.

Speaking of vaccines, here comes China

Flying under the media radar was an article in Foreign Affairs (subscription required) from 5 November by Eyck Freymann and Justin Stebbing. China Is Winning The Vaccine Race: How Beijing Positioned Itself as the Savior of the Developing World is an eye-opening look at China’s herculean effort to rebound from its tragically bungled initial response to COVID-19. From the article:

As a result, the disease spread around the world, crippling economies, killing more than 1.2 million people, and badly damaging Beijing’s image. In 2021, China plans to redeem itself by vaccinating a large chunk of the global population. Although it faces stiff competition from the United States and other Western nations in the race to develop the first vaccine, Beijing is poised to dominate the distribution of vaccines to the developing world—and to reap the strategic benefits of doing so.

Four of the 11 worldwide vaccine candidates are Chinese. The most promising of these, developed by Wuhan-based Sinopharm, is already being given to frontline workers in the United Arab Emirates.

Half the world’s population lives in the developing world, and Donald Trump’s administration, with its America First mantra, has no plans to distribute vaccines to that half of humanity, leaving a wide open door through which China is already walking. Also from the article:

The United States has declined to participate in a World Health Organization (WHO) initiative to deliver two billion vaccine doses to at-risk populations in developing countries, and it has not extended financing to or signed preferential vaccine distribution deals with such countries, as China has done.

While the U.S. will supply vaccines to its own citizenry and sell them to other developed countries, the vast underbelly of humanity will go a-begging. The emerging markets of Asia, Africa, the Middle East, and Latin America can barely afford vaccines, China has seized this opportunity by announcing subsidies and striking loan deals with the eighteen countries where its vaccine candidates are now in Phase Three clinical trials. As far back as May, Chinese President Xi Jinping promised that any successful Chinese vaccine would be used for a “global public good.” Thus far, he has kept that promise.

Throughout the pandemic (and, for that matter, the entire Trump presidency), America has ignored no, stiff armed the half of humanity most in need. This is just another Everest the incoming Biden Administration will have to climb as it tries to undo four years of foreign policy misfeasance, which the Oxford English Dictionary defines as “the wrongful exercise of lawful authority.” Kind of fits, doesn’t it?

Barack Obama returns

President Obama jumped back into the political scene as a force for Joe Biden during the recent campaign. Our first Black president did his part to help rally the African American vote, which proved so consequential in Biden’s victory.

Now, President Obama has written the first book in what will be a multi-book memoir. The Promised Land goes on sale tomorrow. So, he’s begun the book interview marathon, that, in his case, will be widely covered by the media. Case in point Yesterday, he turned up twice on CBS, first with Gayle King on CBS Sunday Morning and second with Scott Pelley on Sixty Minutes.

I’m sure the book is interesting and will sell a gazillion copies, but that’s not what I want to mention here. No, I’d like to end this column with a little story Mr. Obama told at the end of his interview with Ms. King.

Having become a private citizen at 12:01 pm, 20 January 2017, the former president began to reacclimate to private life. For security reasons, he was still prohibited from driving himself. So, as he tells it, there he is in the backseat of some vehicle checking his iPad and being driven somewhere by a Secret Service Officer. Then, the car slows and stops. Since this never happens in a presidential motorcade, he wonders why they stopped. Had something happened? Was there some danger? He looks up and sees the red light. At that moment, another car drives up beside him and he sees children playing in the back seat. As he told Ms. King, “Welcome to private life, Barack.”

Sixty-five days from now, Donald Trump will begin to encounter his own red lights for which he must stop. That will be a reality show worth watching.

 

 

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.