Capitalism is what will defeat Covid

J & J’s journey to the vaccine, from failure to life-saving success, from investment cancellation to advancement, is a little-known story about science, business risk, and innovation. There are also lessons for those who think that capitalism is simply about rapacious profits.

“We would never be in the position we are in today if we hadn’t invested billions of dollars over decades to be able to respond,” says Gorsky, 60, in an interview Monday morning after the FDA cleared his vaccine. Covid. The U.S. Army veteran had been up as early as 3:30 am, participating in one of his morning trainings before the meetings. J & J’s Covid-19 vaccine development over the past year has been a sprint, but the process that led to it has been a decades-long marathon.

Vaccines such as polio, MMR (measles, mumps, and rubella), and seasonal flu are made from weakened or inactivated viruses. But patients often produce a weak immune response to inactivated viruses, and injections using weakened viruses can make immunosuppressed people sick. The manufacturing process is also laborious.

For the past two decades, scientists have been studying a potentially more efficient and effective method known as a “vector vaccine” – using genetically modified viruses to prime the immune system by delivering parts of a pathogen’s genetic code to human cells. Then our cellular machinery makes the dopplegangers. Harmless mimics trigger an immune reaction, which generates antibodies and white blood cells. When the actual pathogen invades, the immune system is primed.

“Your body has multiple layers of response in these situations. There is the immediate answer and there is the longer term answer, ”says Mr. Gorsky. “Your body recognizes the virus and begins to produce antibodies, as well as the T and B cell response.”

B cells produce antibodies that act as sentinels and prevent infection. T cells provide support if a virus penetrates the first-line defense of antibodies and helps the white blood cells go into action. The antibodies may disappear after a few months, but the T cells remain longer and have some photographic memory. Some people who were infected with SARS in 2002-04 were found to have T cells reminiscent of the virus a decade later.

The J&J vaccine was found to be 72% effective in preventing moderate to severe Covid symptoms (meaning two or more symptoms that do not require hospitalization) in US trials. That’s less than 95%. Moderna and Pfizer-BioNTech vaccines, which received emergency use authorization earlier, and are followed by a booster a few weeks after the initial injection. But the trials are not directly comparable. For one thing, the J&J trial occurred later, in the fall and early winter, when more variants of the virus were circulating. Some variants with changes in their spike protein, which helps the virus infiltrate human cells, appear to partially elude the antibody response.

T cells are not so easy to fool. One of the reasons scientists are excited about the J&J vaccine is that its single injection induces a robust T-cell response. This means that immunity is likely to last longer (how much time remains to be seen) and is less likely to be defeated by new variants.

Mr. Gorsky attributes the strong multilayer immune response of the J&J vaccine to his innovative adenovirus-vector platform, AdVac, which he has developed over a decade.

Adenoviruses like those that can cause the common cold, so named because they were first isolated from human adenoids, are easy to manipulate because they have a large genome. Nor do they integrate their genes into ours. This makes them an ideal tool for vector vaccines. The problem is that many people have pre-existing antibodies against adenoviruses from previous infections, so your immune system may try to clear the vaccine like a cold.

In 2007, a promising HIV vaccine from Merck, using adenovirus-5, or Ad5, failed to prevent infection in the later stages of a clinical trial. Worse still, the data indicated that people who tested positive for Ad5 antibodies plus susceptible to HIV infection than people who received a placebo, a phenomenon known as vaccine-induced enhancement. A 2008 article in the Journal of Experimental Medicine was titled “Merck’s Failed HIV Vaccine Study: A Step Backward or Starting Point for Future Vaccine Development?”

It was the last thing. The failure of Merck’s HIV vaccine prompted more studies of other adenoviruses such as Ad26, the vector for J & J’s Covid-19 vaccine. The Dutch biotech company Crucell had been experimenting with Ad26 in a vaccine to prevent malaria and other infectious diseases. Unlike Ad5, antibodies against Ad26 do not appear to sabotage the vaccine. In 2009, J&J partnered with Crucell to develop a vaccine that they hoped would one day prevent infection from all strains of influenza. Two years later, J&J bought Crucell for $ 2.4 billion.

“At the time we had little or no vaccine experience,” says Mr. Gorsky. But capitalism carries risks: Many studies of the Crucell vaccine failed and “we ended up writing a very large part of our initial investment.” Still, Crucell brought with him “two really important technologies that gave seed to what we are doing today.”

One was the AdVac platform. The other was PER.C6 manufacturing technology, capable of mass producing vaccines quickly and inexpensively. Despite previous failures, J&J continued to work on vaccines for Ebola, HIV, Zika, and respiratory syncytial virus, all of which are prevalent in developing countries.

The company has enrolled more than 150,000 patients in vaccine trials for these diseases and last summer the European Medicines Agency approved its Ebola vaccine. Gorsky says that trials for other diseases have made the company confident that its vaccine platform is safe, even among people who have pre-existing immunity to its Ad26 vector.

Conducting trials in the developing world also gave the company’s scientists the confidence and knowledge to conduct global trials of its Covid vaccine. Most of the participants in J & J’s Covid vaccine trial lived outside of the United States: 12.7% in South Africa, 17.3% in Brazil, and 23.3% in five other Latin American countries. Trials in South Africa and Brazil showed that the J&J vaccine could prevent serious illness and death even against newer variants.

“When we discussed the clinical trial sites, and we asked if they could logistically do this, some of our scientists visited them personally and said, ‘They absolutely can do this, and I can answer and validate that they can,’” said Mr. Dice Gorsky. “That is ultimately what put us in a position to be able to run such a high-quality test at that particular time, even in the face of those kinds of challenges.”

J&J was a couple of months behind other vaccine manufacturers, in part because their scientists had to make concessions to create a single-shot vaccine that could be mass-produced and rapidly distributed, even in developing countries. A single dose needed to produce a strong immune reaction, but not a reaction so strong that it causes serious side effects.

“We developed more than a dozen different permutations,” says Mr. Gorsky, “and then we ran them through some initial tests and selected our only candidate that we felt could get the optimal balance.” J & J’s vaccine works by using its AdVac platform to transport the DNA encoding the spike protein on the surface of the coronavirus into human cells.

J&J then worked closely with the FDA and the Advanced Biomedical Research and Development Authority, another federal agency, on clinical trials and distribution. Mr. Gorsky says that in his 30 years working in the pharmaceutical industry, he has never seen so much collaboration between drug manufacturers and the government, with which “we were sharing information in real time.” Drug makers have also joined in: “We all knew that even though we were competing in the market, the real competition here is the coronavirus.”

Merck recently agreed to produce J&J vaccines in its factories. In January, Merck halted development of its two Covid-19 vaccine candidates after early clinical trials showed weak immune responses. Merck’s vaccines used different virus vectors than J & J’s, but one had been shown to be successful against Ebola.

J & J’s vaccine is the third to gain FDA approval, but preliminary results from trials with AstraZeneca and Novavax suggest that they are also very effective. All of these Covid-19 vaccines use innovative technologies that have been developed and tested for decades in other diseases. AstraZeneca’s vaccine is similar to J & J’s, but uses a chimpanzee adenovirus as a vector. The Pfizer-BioNTech and Moderna vaccines inject the genetic code of the virus through mRNA, which instructs human cells to produce pseudopic proteins, which in turn elicits an immune response. The Novavax vaccine uses redesigned spike protein clones.

About 85% of candidate vaccines fail trials, and those that are historically successful have taken 10-15 years to develop. It seems like an incredible stroke of luck and science that we have so many Covid-19 vaccines so soon. But it is more than that. Give credit to years of research and investment by drug makers, as well as government collaboration during the pandemic, which Gorsky hopes will last longer than the pandemic.

“I think this is a golden moment, not just for Johnson & Johnson, but also for the biopharmaceutical industry,” he says. “We fundamentally believe that having a biopharmaceutical and medical technology environment based on the market and innovation is critical in the long term to produce the best overall results for healthcare.”

Ms. Finley is a member of the magazine’s editorial board.