The Durability Study of the Moderna COVID-19 Vaccine is Strange and Unusual

This article is my second attempt to write about this study because the first one vanished while I was trying to save it. Beyond that, there is something quite unusual about this study which I will point out as we go down the article.

The Science magazine published Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants on its September 17, 2021 issue.

The study evaluated the antibody response to the Moderna mRNA-1273 vaccine against the Alpha, Beta, Gamma, Delta, Iota, and Epsilon variants of the SARS-CoV-2.

They tested so by doing three functional assays and two binding assays.

The study group comprises eight volunteers from three age groups -18-55, 55-70, and 71+ years of age who received the two doses of the Moderna mRNA-1273 vaccine.

Blood samples were taken and sampled at four-time points. 4 weeks after the first
dose and two weeks, three months, and six months after the second dose (days 29, 43, 119, and 209 after the first dose, respectively)

Here is the study’s conclusion from their abstract.

By analyzing sera obtained 6 months after the second shot in the primary vaccine series, the researchers found that neutralizing antibody titers persisted against all variants tested.

However, neutralizing antibodies against the B.1.351 variant had dropped considerably by 6 months, and some individuals had weak, and in some cases no, neutralizing activity

Note: B.1.351 is the Beta variant.

Although this study involved several variants, the main variant to focus on is the Delta variant, also called B.1.617.2. That’s because the Delta variant of the SARS-CoV-2 is now the predominant cause of COVID-19 here in the US. According to the CDC COVID Data Tracker on its latest 9/19/2021- 9/25/2021 report.

The bar graph below compares the percentage of variants from June 2021 to September 2021. The Delta B.1.617.2 is orange.

The Delta variant is the cause 98-99% of all COVID-19 in all ten regions of the US,

Since we are in a pandemic, let’s include other countries. Below, the Delta variant causes 100% of COVID-19 in several countries. The graph below is from ourworldindata.

By now, some would be asking. I hope the Moderna vaccine is effective against the Delta variant!

We go back to the study. Below is the tabulated report of six different assays to test the presence and effectiveness of antibodies produced in response to two doses of Moderna vaccination against several variants.

TIP: When you look at the table below, look for B.1.617.2. That is the Delta variant.

Did you notice that the Delta variant (B.1.617.2) is missing from Live Virus Neutralization, ACE2 Competition, S-2 Binding, and RBD Binding? Four out of six assays. What is going on?

I will unpack the different tests to know why the data about the Delta variants should be there.

Pseudovirus Neutralization -Pseudoviruses are created in the laboratory by inserting genetic material into a human cell. Pseudoviruses are safer when studying viral interactions, especially if they are contagious, like the Delta variant.

Looking at Pseudovirus Neutralization from the table, we see that detectable antibodies are still present on Day 209 or six months for all the variants. However, the Beta variant (1.351) is the lowest. The antibodies for the Delta variant (B.1.617.2) are still very high at 96%. – The findings of the Pseudovirus Neutralization is the meat of the study—the main course.

Note: Good studies usually include other experiments to give more substantial support to the results. Supporting experiments show repeatability, consistency, and due diligence —all for the credibility and strength of the conclusion.

Data about Live Virus Neutralization and ACE2 competition against the Delta variant would have made the study more robust. After all, it is a survey about the effectiveness of antibodies induced by the Moderna vaccine.

Live Virus Neutralization is when they test an actual virus against an antibody. In this study, Live Virus Neutralization was done for the Wuhan (WA1), D614G, Alpha (B.1.1.7), and Beta (B1.1351).

The Wuhan SARS-CoV-2 is the original virus and is exceptionally infectious and deadly. Their laboratory is equipped for biosafety. They have the blood sample to test against the Delta variant. So why is the Delta data not there?

ACE2 Competition Assay tests whether the presence of an antibody can prevent the virus from attaching to the ACE2 receptor. It is an essential functional assay because it evaluates the antibody almost in real life. Again, the results about the Delta variant are missing.

Binding Assays

Binding assays are a measure of the presence and extent of the binding of two molecules. S-2P Binding and RBD Binding, and Cell-Surface Spike Binding are binding assays. This study checked the binding of the antibodies generated by the Moderna vaccine against the different parts of the SARS-CoV-2 spike protein.

Vaccination brings out more than one antibody. There are different types produced. Some are not as useful as others.

We want to find out if the antibodies attach to the specific part of the spike protein that is involved and initiates infection. If you stop the disease from the beginning, then that vaccine is a resounding success.

We will look at the parts of the spike protein and see what is the most important. Let’s begin with the coronavirus image below. The spike protein are the projections coming out of the middle part.

If we get one spike protein, we can see the different parts. See the electron microscopy of the Spike protein below. Readers of this website are familiar with it.

The magenta on top is the receptor-binding domain RBD. The RBD binds to the ACE2 receptor and is the most crucial part of the spike protein in vaccine making.

Neutralizing antibodies are antibodies elicited by the vaccine that can attach to the RBD, preventing that virus from adhering to the ACE2 receptor. There is no viral entry once the virus cannot bind to the ACE2 receptor, and infection does not happen.

Back to the study, the data about the RBD Binding of the Delta variant is not there. That’s a bummer. If the RBD binding data is there, that would have explained the neutralization. Below is part of the larger table above. Look at the glaring absence of B.1.617.2.

Spike Protein-2 or S-2 P Binding

The spike protein-2 is the orange and turquoise in the spike protein above.

The numbers for the Delta variant are also absent for the Spike protein-2 binding measured as S-2 Binding. The spike protein-2 participates in viral attachment in a supporting role. It changes the shape of the spike from a “close” to an “open” position when it is ready to attach to the ACE2 receptor.

Since the antibodies involved are not directly involved in preventing attachment to ACE2, the antibodies to the spike-protein-2 are called non-neutralizing. Non-neutralizing antibodies are good to have, but only if the neutralizing antibodies are high. Then they work together to prevent infection.

If there are more non-neutralizing antibodies than neutralizing antibodies, there is a risk of severe infection rather than infection prevention if the vaccinated person gets exposed to the SARS-CoV-2 again.

The condition where the disease is enhanced rather than prevented is called antibody-dependent enhancement (of infection). High or low, that data would be valuable. It is disappointing that the values of the antibodies to the Delta variant in S-2P binding are also absent. See below for an article on antibody-dependent enhancement).

Instead, they have the Wuhan (WA1), Alpha (B1.1.7), Beta (B.1.351), and Gamma (P.1) that are presently irrelevant to the pandemic.

The only other part where the Delta variant is mentioned in the table above is the Cell-Surface Spike Binding, which measures the antibodies attaching to the whole spike protein. In the table, the antibodies to the Delta variant are 100% at six months which is OK but are those antibodies attaching to the receptor-binding domain? Are they neutralizing? They must be because the Pseudovirus Neutralization data about the Delta variant says so, but where is the backing evidence?

Unfortunately, the supporting evidence in the paper is relatively thin.

A curious interview

The day before the paper was published, CNBC interviewed the president of Moderna, Stephen Hoge. Here is a quote of what he said,

Delta is “just so good at infecting people and replicating that it raises the bar on how good vaccines have to be.

The fast-spreading delta variant is so contagious, it’s exposed weaknesses in vaccine protection and changed the outlook for ending the pandemic

“It’s actually shown some of the weaknesses that [vaccines] have earlier than you might expect.”

Wait! What? He’s talking about the Moderna vaccine. I thought their Pseudovirus Neutralization Assay was 96% at six months. There is not even a downward trend. What vaccine weaknesses is he referring to?

What does the president of Moderna know that is not in the study?

Competing Interest Declarations

Never mind that two of the authors are employees of Moderna, and one is on the board of Moderna. And the other authors are holders of patents on vaccine making and reports grants from several pharmaceutical companies.

Below is copied and pasted from Competing Interest Declarations. It can be found at the end of the study.

H.B. and B.L. are employees of Moderna, Inc. M.S.S. is on
the Advisory Board of Moderna, Inc. B.S.G. and K.S.C. are inventors
on international patent application no. WO/2018/081318 entitled
“Prefusion Coronavirus Spike Proteins and Their Use” and pending US patent application no. 62/972,886 entitled “2019-nCoV Vaccine.”
P.C.R. and J.H.B. report a pending US patent application no. 63/
025,918 entitled “Coronavirus RNA vaccines and methods of use.”
E.A. reports grants from Merck, PaxVax, Micron, MedImmune,
GSK, Pfizer, Janssen, and Sanofi-Pasteur. E.A. reports personal fees
from Pfizer, Janssen, Sanofi-Pasteur, Medscape, and Kentucky
Bioprocessing, Inc., outside the submitted work. N.G.R. reports grants
from Pfizer Merck, Sanofi-Pasteur, Eli Lilly, and Quidel, outside the
submitted work.

Never mind that they have conflicts of interest. I’m sure they also produce objective studies that can pass peer-review and the editorial board of the Science Magazine.

Check this out: Durable Immunity from Pfizer COVID-19 Vaccine Lasts only Six Months

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Related:

Featured study:

PEGU et al. Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants. SCIENCE. 17 Sep 2021. Vol 373, Issue 6561. pp. 1372-1377. DOI: 10.1126/science.abj4176

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