Defeating Infectious Agents — 4

The current flu vaccine is quadrivalent, meaning it only targets two type A and two type B strains. To override these challenges, there has long been the dream of a universal flu vaccine that would target all twenty subtypes of influenza A and B. The mRNA nanoparticle platform has been applied to this objective, with inclusion of twenty encoded antigens targeting each subtype, achieving high neutralizing antibodies and strong protection in multiple experimental models. The attention to atomic-level structure of flu antigens has led to a new ability to generate broad neutralizing antibodies, a path toward a potent and durable influenza vaccine. We’re not there yet, but there is intensive effort by several companies, including Moderna, Osivax, Centivax, and Pfizer, who are pursuing a far better universal flu vaccine in ongoing clinical trials.

Structure-based vaccine design is now being used to develop a hepatitis C virus vaccine. The pathogen behind this disease was first identified in 1989, tied to chronic liver disease and liver cancer, killing approximately three hundred thousand people each year of about fifty-eight million people infected around world. But the hepatitis C story isn’t just about vaccines. It is also about failing to prevent it. As Francis Collins, the NIH director from 2009 to 2021, mentioned when he wrote about the death of his brother-in-law, we’ve had curative antiviral pills since 2014. Of the more than 2.4 million Americans who have been infected with hepatitis C, 40 percent don’t know it, and 75 percent of infections progress to a chronic form. That’s why screening for hepatitis C is essential. The virus leads to slowly progressive scarring of the liver, leading to cirrhosis, liver failure, or liver cancer. Fifteen countries, including Canada, Australia, and Egypt, are on track to eliminate hepatitis C this decade with major national screening and treatment campaigns, but the United States lags far behind. Thus far, not mounting such efforts or squarely addressing the medication’s cost and access, the opportunity to eradicate hepatitis C has been squandered.

Pre-COVID, the three biggest infectious disease killers were malaria, tuberculosis (TB), and HIV, and all are being pursued by clinical trials with mRNA nanoparticles. Malaria was identified as a pathogen in 1880; only in recent times have we started to see successful structure-based vaccines get approved for protection in children, the first vaccine directed against a parasite. Although there are some new drug candidates that we hope will add to the armory in our battle with TB, we’re still without a vaccine and have been since the pathogen was identified in 1882. It kills 1.4 million people each year. Now, two different mRNA vaccines against TB are in clinical trials, one of which (M72/ASO1E, Glaxo Smith Kline) is in the final stages and provided 50 percent protection against lung TB in people actively infected.