What's Old is New and What's New is Dead

Ask not for whom the bell tolls, it tolls for mRNA vaccines

Another day, another assault on vaccines and pandemic readiness in America. US Health and Human Services Secretary Robert F. Kennedy, Jr. announced that he was terminating $500M worth of contracts at the Biomedical Advanced Research and Development Authority (BARDA) to develop new mRNA vaccines, including those targeting H5N1 bird flu.

As usual, Kennedy claimed this decision was informed by experts after a thorough scientific review. Also as usual, Kennedy lied.

God help the vaccine that gets evaluated by this review panel

mRNA vaccines do not “fail to protect effectively against upper respiratory infections like COVID and flu.” In fact, studies estimate that millions of lives were saved by COVID vaccination. mRNA vaccines, like many other vaccines, are not completely sterilizing (they don’t prevent infection). However, there are very few vaccines that provide completely sterilizing protection against respiratory viruses. That doesn’t mean they don’t work.

It’s great when vaccines can stop infection, but that isn’t their primary purpose. The first vaccine is actually a virus. The story goes that Edward Jenner, an 18th century physician in rural England, observed that milkmaids didn’t get smallpox and instead had (really attractive sounding) crusty pox lesions on their faces. So he scraped those lesions off a milkmaid’s face and inoculated a young boy, then challenged him with smallpox. Turns out the milkmade face lesions were caused by vaccinia virus infection, acquired from the cows (vaccinia is from vacca, which is Latin for cow and also where the word “vaccine” comes from). Vaccinia is an orthopoxvirus that elicits immune protection against variola virus (smallpox). But Jenner had no idea about that, because he didn’t know what viruses were. He observed disease—the mild milkmaid face disease caused by vaccinia virus infection and the severe disease smallpox caused by variola virus infection. Jenner used vaccinia virus to prevent disease, not infection.

Vaccines that prevent disease are not failures. They are very successful. Authentic vaccination—vaccinia virus infection—eradicated smallpox. Public health history is filled with incredibly successful vaccines that prevent disease but don’t prevent infection. The tetanus vaccine doesn’t prevent infection at all, but it completely prevents tetanus. The Salk inactivated polio vaccine doesn’t prevent poliovirus infection and the Sabin live attenuated polio vaccine actually is a poliovirus infection, yet both of these vaccines freed entire generations from growing up in iron lungs. Flu shots don’t prevent flu, but they have kept millions of people out of the hospital and out of the morgue. There are millions of people who are alive now that wouldn’t be without COVID mRNA vaccines.

I can only imagine the types of experts that Kennedy supposedly listened to on this issue. He has installed multiple anti-vaxxers who specialize in mRNA vaccine antipathy throughout HHS. On the Advisory Committee for Immunization Practices (ACIP), he could get distinguished mRNA haters Robert Malone or Retsef Levi to weigh in on how the spike protein is cytotoxic (it’s not) or how mRNA stays in the body and eventually kills you (it doesn’t). Over at FDA, Tracey Beth Høeg could go over her portfolio of shitty preprints that she claims show mRNA vaccines cause myocarditis and are dangerous for children (the risk of myocarditis from COVID is much higher and mRNA vaccines are safe). At NIH, Principal Deputy Director Matthew Memoli could explain how diligently he has worked to suppress mRNA vaccine research already.

Kennedy elaborated on his expert view in this announcement, where he confidently showcased his ignorance of how viruses, vaccines, or immune responses work. Brace yourself for some immuno-gibberish:

But as the pandemic showed us, mRNA vaccines don’t perform well against viruses that infect the upper respiratory tract. Here’s the problem, mRNA only codes for a small part of the viral proteins, usually a single antigen. One mutation and the vaccine becomes ineffective. This dynamic drives a phenomenon called antigenic shift, meaning that the vaccine paradoxically encourages new mutations and can actually prolong pandemics, as the virus constantly mutates to escape the protective effects of the vaccine.

mRNA vaccines encode an antigen (a protein that elicits immune responses). For the COVID vaccines, this is the spike protein. They can be monovalent (against a single antigen) or multivalent (against more than one antigen). They can encode for part of a protein or the entire thing. Antibodies bind all over these antigens and T cells can recognize many different parts of the antigens, as well. That means that a single mutation—which would change one amino acid in the protein—is very unlikely to have an effect on overall immunity. If one antibody can’t bind the mutated part of the protein, there will be other antibodies that can bind the antigen everywhere else. One mutation does not render vaccines ineffective. Even a hundred mutations do not render vaccines ineffective. When omicron emerged, original recipe vaccines were less effective, but they were not completely ineffective. They still provided protection against severe disease, as they were designed to do.

I’m not sure where Kennedy picked up the term “antigenic shift,” but it’s clearly not from reading the literature on influenza virus evolution where it originated. Antigenic shift usually refers to a drastic, rapid change in flu antigens caused by reassortment. It absolutely does not refer to vaccines encouraging new mutations and prolonging pandemics, because vaccines don’t do that. Viruses acquire mutations when they replicate and they replicate when they spread to new susceptible hosts. They are most likely to spread to unvaccinated or immune naive hosts, because they have no pre-existing defenses against them. If you don’t want to prolong a pandemic, then you want to avoid having a large population of susceptible people that will facilitate unchecked transmission and viral replication. Even vaccines that don’t produce sterilizing immunity reduce viral replication (the infection gets cleared more quickly) and transmission (there is a higher barrier to establishing an infection). Vaccination discourages new mutation and ends pandemics.

As always, Kennedy gave his usual “vaccines are great, I just care about safety” disclaimer and implied that mRNA vaccines have a weak safety record. That’s also not true, unless you’re reading the shoddy anti-vax crap that Høeg churned out for most of the pandemic or talking to NIH Director Jay Bhattacharya or FDA Commissioner Marty Makary, both of whom have repeatedly made baseless claims about mRNA vaccine safety.

This is my favorite part, where Kennedy explains what “evidence-based, ethically grounded solutions” BARDA will focus on instead of mRNA vaccines: “whole-virus vaccines.” This likely refers to his $500M payout to Memoli and Acting NIAID Director Jeffrey Taubenberger to make a quadrivalent inactivated whole-virus “universal” flu vaccine that has been christened Generation Gold Standard. Not only is this vaccine technology old-timey enough to have been developed by Jonas Salk, it is less effective than mRNA vaccines, at least for COVID. Inactivated whole virus vaccines also don’t produce sterilizing immunity.

Whole virus vaccines are also slower and more dangerous to produce. Unlike mRNA vaccines, which can be rapidly synthesized without any virus at all, to make whole virus vaccines you actually have to grow up a ton of virus so you can inactivate it. Considering Kennedy’s fear of lab leaks and hostility toward virology in general, it’s a little surprising that he thinks it’s safer and more “ethically grounded” to grow up a shitload of H5N1 flu to make a vaccine that is demonstrably less effective than the mRNA platform. In a pandemic situation, you would need 9 months to a year to manufacture whole virus vaccines for use at population scale. mRNA vaccines, on the other hand, could begin production the day that you have an antigen sequence. mRNA vaccines can be rolled out much more quickly, in a matter of 2-3 months. During an epidemic or pandemic, those months directly translate to people’s lives.

Kennedy continues to demonstrate that he is a staunch proponent of deadly pathogens who will not rest until he destroys vaccination altogether. There is no reasonable argument for terminating research on mRNA vaccines, particularly for pandemic potential respiratory viruses, in favor of dated platforms that are less effective, less rapid, and less safe to produce. As with all of his vaccine policy decisions, this one will make America more vulnerable, less capable of responding to infectious disease outbreaks, more sick, and more dead. Killing mRNA vaccine development will kill people. Those lives are what Kennedy must be accountable for.