Everything you ever wanted to know about vaccines

I honestly think this latest from Katherine Wu is the best article I’ve yet read on vaccines.  It is ostensibly about the potential for J&J to be a bit of a darkhorse success (it may provide more durable immunity), but it hits pretty much everything we know and don’t know about vaccine types, number of doses, spacing of doses and the all-important concept of vaccine durability.  So good.  Also, I must say, it does have me feeling great about my combination off J&J plus Moderna.  If you have even a modest interest in vaccine science and human immunity, it’s a must read.  And if you don’t, here’s what I found to be the most interesting points to foist upon you:

This incessant ragging has been all too easy—and maybe shortsighted. According to some experts, the haters are overlooking a trait that could rescue J&J’s reputation, and possibly even keep it in scientific contention. “I think there is a silver lining to this vaccine that a lot of people don’t see,” David Martinez, an immunologist at the University of North Carolina at Chapel Hill who is studying immune responses to COVID-19 shots, told me. It’s a trait called durability—the ability of a vaccine’s protection to persist, despite the ravages of time. Several researchers, including representatives of the company that designed the J&J vaccinesay they’re seeing early hints of this with the shot. “It’s unequivocal,” Mathai Mammen, the global head of research and development for Janssen, the vaccine-manufacturing pharmaceutical company owned by Johnson & Johnson, told me. In tracking the vaccine’s effectiveness, “there is no change, month over month over month.” The shot’s initial magnitude of protection against sickness might not match Moderna’s or Pfizer’s. But after they’re built, J&J’s defenses seem to stick around in a way that their mRNA-driven counterparts might not, like a low-wattage bulb that keeps burning, long after all the other lights in the room have flickered and died…

As the pandemic heads into its third year, durability underpins some of the biggest open questions in COVID immunology—the long-term outlook for our current shots, the number we’ll ultimately need, and the possibility of engineering an even sturdier vaccine. A lack of durability might mean we’ll be getting COVID shots often, maybe even annually. Or, if we can figure out a clever way to give out shots now, we may not have to administer them again. A vaccine’s value isn’t just in its peak performance; also essential to know is when, and how quickly, protection might start to decline…

But the quest for durability has long been thorny. Several experts I spoke with described it as one of the most elusive concepts in vaccinology, an immunological white whale that researchers frequently chase but almost never catch. “We don’t have one right answer” for what makes a vaccine’s protection stick, Padmini Pillai, an immunologist at MIT, told me. “It’s always it depends.” …

Establishing durability starts with first impressions. To offer truly long-lasting protection, a vaccine has to persuade the body to study its offering, then stably store that intel away. “The bottom line is, you have to convince the immune system that this is scary,” Mark Slifka, an immunologist and vaccine expert at Oregon Health & Science University, told me. When the process works well, it can work really well. Every time a microbe returns to trouble us, the defenses we mount against it get stronger, faster, more precise; the response becomes a reflex, built on the memories of immune cells that have thwarted the same threat before.

The major players in immune memory fall into two main camps, headlined by B cells and T cells. B cells are weapons manufacturers, tasked with pumping out microbe-trouncing antibodies; T cells are single-combat assassins that home in on infected cells and force them to self-destruct. Both Bs and Ts will show up to fight most infections of note, cloning themselves into complementary armies. As the danger passes, their numbers contract, leaving behind only a so-called memory contingent—dormant Bs and Ts that holster the capacity for protection, like sleeper agents waiting to hear a trigger phrase. And finding relatively sturdy levels of these cells and the molecules they make is a decent proxy for judging immunity’s longevity. High levels of antibodies and B cells that recognize the viruses responsible for smallpox and measles, for instance, have been found in people decades after they received those two very potent vaccines.

When investing resources, though, our immune systems must be stingy. Not every potential threat they encounter gets locked in the body’s defensive memory. Generally speaking, they’ll devote more storage space to bugs they deem dangerous repeat offenders. Many durable vaccines, then, are really annoying ones, pestering cells so much that they have little choice but to remember what’s up…

When defenses drop, though, they tend to do so stepwise: The strongholds against infection fall first, then transmission, then serious disease, and finally death. Pfizer’s effectiveness against milder COVID cases, and probably transmission, gradually but notably ebbs in the months after people are inoculated. Some of that dip is probably attributable to fast-spreading, slightly immune-evasive Delta, and the world’s growing ennui with distancing and masks; if a new variant like Omicron rises, we could be due for yet another trough in protection. But decreasing effectiveness could also reflect our bodies’ reaction to the shots. Antibodies seem to be tied tightly to protection thresholds, and “we’re quickly seeing antibody levels fall” in the months after people get their Pfizer and Moderna shots, Ai-ris Yonekura Collier, a physician and immunologist at Beth Israel Deaconess Medical Center, in Boston, who’s been studying immune responses to COVID-19 shots, told me.

That in and of itself isn’t catastrophic—antibodies always contract after the first flush of infection or vaccination—but the slope is steeper than some researchers would like. In a small, recent study, Collier and her colleagues showed that about eight months post-vaccination, virus-blocking antibodies are down roughly 40-fold from their peak, and it’s not clear when or where the downslope will flatten into a plateau. Perhaps the molecules have already settled at a stable level, with safeguards against severe disease strong, and defenses against milder outcomes middling. Or maybe they’ve still got a ways to fall. “It’s normal to see rapid decay,” Slifka told me. “The question is, how high above the protective threshold do you land?”

Okay, that’s a lot.  And there’s a lot more really good stuff in there.  Like the fact that the HPV vaccine is an absolute durability champ.

I also appreciated how this was a nice thorough article which fit so well with what my virologist friend has been trying to explain to me in online conversations.  Anyway, it certainly makes clear the benefit of being boosted.  And if you are reading this, you almost certainly are.

 

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