To Vaccinate or Not---The Rat Flu Odyssey Continues
From Katelyn Jetelina
The FDA and CDC authorized the bivalent boosters based on a number of data sources. This was necessary to get ahead of the virus, like we do with the flu vaccine each year. Our hope is that a bivalent booster will help in three distinct ways:
Greater protection against infection and transmission, by boosting our first line of defense—neutralizing antibodies;
Longer protection against infection and severe disease, even just by a few months. (Unfortunately, we are at the mercy of time to know whether this will happen, but we are hopeful given data from our bivalent Beta vaccine clinical trials);
Broader protection or the ability to create antibodies that “see” more virus parts and “attach” more strongly compared to the antibodies we have right now.
We have two new studies with promising data.
The first preprint solidifies #1 and #3. Before now, we’ve relied on mice data to show that bivalent BA.4/5 vaccine increased neutralizing antibodies. But, now we have data on humans. Scientists measured antibodies in individuals who had three mRNA vaccines and a BA.4/5 breakthrough infection. (This can act as a proxy for the BA.4/5 booster.) They found antibodies were very high and were high against all Omicron subvariants studied. In other words, the bivalent booster will enhance protection against Omicron, which will help prevent infection and transmission. This is not surprising, but reassuring.
The second preprint points to #3. This is a study we’ve all been waiting for. Scientists studied B-cells—our antibody factories—and, particularly, whether we could make new B-cells (update the factory line after seeing another variant). This is important to study to ensure we don’t have original antigenic sin. (If you haven’t already, read this previous post on original antigenic sin where I attempt to explain this concept.) The current study showed that while we do have imprinting (which is normal and expected), we do make new B-cells after an updated Omicron vaccine. In fact, the authors stated, “immunization with an antigenically distant spike can overcome the antigenic imprinting by the primary vaccination series.” This means that an updated booster will increase the diversity of our antibodies and that memory will be retained by our immune systems.
Limitations
It’s important to note that, unfortunately, new subvariants of Omicron are already on the horizon with concerning mutations for antibody escape, like BA.2.75.2 or BQ.1.1. These new variants were not tested in the studies above. We’ve seen from another study that these new variants can substantially escape neutralizing antibodies from Coronavac (a Chinese vaccine using inactivated virus). But there are still a lot of unknowns: We don’t know how mRNA vaccines will hold up; we don’t know if these variants will take hold; and neutralizing antibodies are just one part of our complex immune system. Our safest bet is not through infection, but through vaccination. Our immune systems need updating and we need to be responsive to that, even if that updating is not perfect.