Does bivalent work better than monovalent? Industry vs. Academic research, whom to trust more? (Studies)
Let’s have an update on the bivalent vaccine human immunological data. Is the bivalent vaccine really better than the monovalent vaccine, like the manufacturer have said, or is it just another similar product that may have wasted taxpayer’s money? Let’s find out with real data.
- Slow uptake of Bivalent vaccine uptake
It is not a secret that Americans are not very eager about getting the bivalent booster vaccine. According to some of the latest official statistics, only about 15 million people have received the new bivalent booster, compared to about 111 million people who received the original monovalent booster. For most of them, that was their third dose.
But why the slow uptake?
I don’t think I need to explain too much. To sum up, primarily because of general vaccine fatigue, people are just tuning out from the COVID and vaccine topics on various media, including here on my channel. Second, many people, including my family, have recently had COVID and were presumably infected by the BA.5 omicron subvariant. The symptoms were mild and did not appear to have any lasting symptoms.
Nationally, the number of reported cases continued to decline, and most of the population has acquired some level of immunity from vaccines or infection. The perception of risk for hospitalizations and deaths has decreased, especially among people with normal immune function and without chronic illnesses.
- Sub-par vaccine communication
Many officials have tried to persuade the public to receive the bivalent booster. But they are not very effective, mainly because they only present a qualitative argument.
For example, the new booster can reduce some Omicron new infections and transmission, but the actual number is murky. Even though the industry presents some quantitative antibody titer levels, there is a lack of evidence to precisely translate an immunological response into clinical efficacy.
Is the antibody level the higher, the better?
In contrast to the belief that the higher, the better, a recent pre-print study done by a collaborative research team of biotech companies and the Washington State University reported antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers.
(https://www.medrxiv.org/content/10.1101/2022.10.18.22281172v1.full.pdf)
They showed that a 1:30 monoclonal antibody dilution provided about 50% protection against symptomatic COVID in adults without prior immunity. They also modeled that a low level of serum neutralization antibody from vaccine-induced polyclonal antibody supports a similar 50% protection.
It is important to note that the study did not suggest that a low level of antibody can provide absolute protection. Similarly, there are also people with a high level of neutralizing antibodies from recent boosters contracting COVID.
I also have two personal friends who just got COVID this past week after receiving their bivalent boosters not too long ago. In other words, there isn’t an absolute threshold of protection from a high antibody titer level.
The bigger implication is that both vaccine and infection-induced immunity against COVID is a combination of other mechanisms in addition to neutralizing antibodies, such as T cells, memory B cells, non-neutralizing antibodies, and innate immunity.
Unfortunately, even after almost two years of the mass vaccination campaign, the majority of the focus is still on neutralizing antibodies.
That’s an area that needs to be improved.
- Industry Antibodies vs Academia Antibodies
Since we are on the antibodies, let’s compare data from the industry and academia. Antibody titers is the easiest way to assess immunological response against the SARS-CoV-2 virus.Both Pfizer and Moderna presented antibodies titer to get regulatory agency authorization for their bivalent booster.
The official language still believes the bivalent booster will be better than the monovalent booster. It is not surprising, considering they have invested so much taxpayer’s money in the new booster.
The vaccine manufacturer is also in agreement. Moderna published their BA.1 bivalent booster immunological result in NEJM in early October. The study reported that the new BA.1 booster granted a better antibody response to the Omicron variant and is equally well against the ancestral SARS-CoV-2 compared to the monovalent booster.
But when we looked closely at their published data, people with previous infections who received a monovalent booster had a superior neutralizing antibody response than those without previous infections receiving the new booster.
With so many people having had both symptomatic and asymptomatic Omicron infection in 2022, is the new bivalent vaccine really clinically superior to the monovalent booster?
That’s literally a multimillion dollars question that no one has a certain answer. But the taxpayer money has already been spent.
Two pre-print studies posted near the end of October have cast some doubt on the official and industrial belief of the superiority of the BA.5 bivalent booster.
A research team from Harvard University evaluated humoral and cellular responses in fifteen individuals who received the original monovalent mRNA booster and in eighteen individuals who received the BA.5 bivalent mRNA boosters.
Both CD8 and CD4 T cell responses increased only modestly following monovalent and bivalent boosters. Median BA.5 CD8+ T cells went from 0.027% to 0.048% with the monovalent booster and from 0.024% to 0.046% with the bivalent booster. Similarly, CD4+ T cells went from 0.06% to 0.13% with the monovalent booster and went from 0.051% to 0.072% with the bivalent booster. We don’t know what these small increases translate to actual protectiveness.
In terms of neutralization antibodies, both monovalent and bivalent boosters stimulated a marked increase. Even though the bivalent booster had a 1.3 times higher level than the monovalent booster, that level was not statistically significant. When immunological data is not significant, it is even harder to make clinical translation predictions.
The second preprint was done by a research team from Columbia University. The researchers used pseudovirus neutralization assays to measure the effect of neutralizing antibodies collected from people who received the bivalent booster as the fourth dose, people who received three or four doses of the original monovalent vaccine, and people who had BA.4/5 infection after mRNA vaccination.
At ~3-5 weeks post booster shot, individuals who received a fourth vaccine dose with a bivalent mRNA vaccine targeting BA.4/BA.5 had similar neutralizing antibody titers as those receiving a fourth monovalent mRNA vaccine against all SARS-CoV-2 variants tested, including BA.4/BA.5.
Interestingly, those who received a fourth monovalent vaccine had a slightly higher neutralizing antibody titer than those who received the bivalent vaccine against three related viruses: SARS-CoV, GD-Pangolin, and WIV1.
The conclusion is that the bivalent booster given as the fourth dose did not induce superior or higher neutralizing antibody responses in humans.
(https://www.biorxiv.org/content/10.1101/2022.10.22.513349v1)
- The Problem
So again, we have opposing narratives and evidence about the bivalent booster’s superiority. White House Officials continue to believe the industrial data more than work from academia, arguing the academic studies had a small sample size.
The reality is that studies from the industry will always be bigger than those from academia. But there is also an apparent competing interest from the industry. They must sell their products.
In case you don’t know, after the FDA gave EUA to the new bivalent booster, all the old monovalent boosters were no longer legal to use in the US. But remember, taxpayers had already paid for all the old monovalent vaccines. Where did they go? I couldn’t find any information on that. Were they being donated to other countries, or were they simply going to the dumpster?
If a new product is better than the old one, then it is logical to buy the new one. But if the improvement is questionable or marginal, is that a wise way to spend taxpayer money? Or is it just a way to guarantee profits to the big pharmaceutical industry?
