October 6, 2022

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Moderna three COVID-19 mRNA vaccines immunized mice data

Moderna three COVID-19 mRNA vaccines immunized mice data



 

Moderna three COVID-19 mRNA vaccines immunized mice data

 


On February 2, 2022, Michael S. Diamond published an article in Science Tanslational Medicine: Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains: Comparing Moderna in mouse models (129S2 and K18-hACE2) The immunogenicity and protective effect of preventing VOCs of three new coronavirus mRNA vaccines designed, these three mRNA vaccines include mRNA1273 (based on the new coronavirus original strain Spike), mRNA1273.351 (based on the new coronavirus beta variant Spike), mRNA1273.211 ( Bivalent, half the original Spike general Beta variant Spike).

 

The serum antibody titers of the immunized mice were detected, and it was found that the high-dose (5ug) and low-dose (0.25ug) groups of the three vaccines could strongly stimulate the production of serum neutralizing antibodies targeting the test VOCs, and the three vaccines stimulated the production of neutralizing antibodies.Serum neutralizing antibody titers targeting the Delta variant were lower compared to other VOCs .

 

The mice in the high-dose groups of the three vaccines had very good preventive and protective effects against the tested VOCs in the lungs. However, in the low-dose group immunized mice, serum neutralizing antibody titers decreased by orders of magnitude, and breakthrough infections occurred in the lungs.

This suggests that individuals vaccinated with the three vaccines may develop breakthrough infections when faced with certain VOCs variants, such as Delta.


Next, let’s take a detailed look at the immunogenicity and preventive effect of these three vaccines in mouse models.

 

 

 

Serum binding antibody titers


In 129S2 mice, 2 doses of the three vaccines and the control group ( invariant coding antigen ) were respectively inoculated, and serum was collected 3 weeks after the second injection.

ELISA showed that both the high-dose group ( 5ug ) and the low-dose group ( 0.25ug ) could strongly stimulate the production of sufficient anti-Spike-IgG binding antibody titers. The IgG-binding antibody titers of the Spike-targeted VOCs variant in the serum antibodies triggered by each vaccine were similar.

 

Moderna three COVID-19 mRNA vaccines immunized mice data

 

 

 

Serum neutralizing antibody titers


Neutralizing antibody titers in sera of 129S2 mice vaccinated with the three vaccines were determined by FRNT (live virus):

 

(1) Compared with the unvaccinated mouse group , the high-dose vaccination group can strongly trigger serum neutralizing antibody responses targeting test VOCs. and antibody titers are basically similar ( except that between individual vaccines, there is a 4-2-fold difference in serum antibody titers targeting the same VOC ).

It is worth noting that the Delta-targeted serum neutralizing antibody titers triggered by the three vaccines were significantly lower than those targeting other VOCs ( 4-5 times ).

 

(2) For the low-dose vaccination group, compared with the high-dose group, the serum neutralizing antibody titers of the three vaccine-triggered targeted test VOCs were reduced by almost an order of magnitude . At the same time, the three vaccines targeted the same VOC.

There are obvious differences in the serum neutralizing antibody titers of the VOCs , and it can also be seen that the antigen mixed bivalent vaccine ( mRNA-1273.211 ) targets VOCs The serum neutralizing antibody titer is always the same as that of one of its components, the monovalent antigen vaccine ( mRNA -1273.211). -1273/mRNA-1273.351 ) close.

Compared with mRNA-1273, vaccination with mRNA-1273.211 triggered a 4-fold reduction in serum neutralizing antibody titers targeting WA1 D614G. Interestingly, the Delta-targeting serum neutralizing antibody titers triggered by the three vaccines at low doses were still significantly lower than those targeting other VOCs, and the Delta-targeting serum mRNA-1273. And antibody titers were again significantly lower than those triggered by mRNA-1273 ( 3.3-3.6-fold ).

 

Moderna three COVID-19 mRNA vaccines immunized mice data

Determination of serum neutralizing antibody titers targeting various VOCs in vaccinated 129S2 mouse serum by FRNT

 

 


Serum Antigen Profile


Using serum neutralizing antibody titers to draw serum antigen maps can more intuitively display vaccine-triggered serum antibody titers targeting various VOCs and the differences in VOCs antigens ( red squares indicate inoculation with mRNA-1273 serum, blue squares indicate inoculation with mRNA-1273 serum mRNA-1273.351 serum ):


(1) WA1/2020D614G clustered with WA1/2020D614G/N501Y, while B.1.351 clustered with B.1.1.7/E484K, and VOCs clustered together to represent antigenic similarity.

 

(2) B.1.617.2 has the most distant epitope , which is consistent with the lower neutralizing antibody titers targeting this VOC variant triggered by the three vaccines .

 

(3) The antigen map showed some differences between the high dose and the low dose: in the high dose group, B.1.617.2 was at the same distance from inoculation with mRNA-1273 and mRNA-1273.351, indicating that serum neutralizing antibodies escaped from the two vaccines. The ability of B.1.617.2 to move to the left and a little further from mRNA-1273.351 in the low -dose group , indicating the ability to escape neutralizing antibodies in sera triggered by mRNA-1273.351 than in sera triggered by mRNA-1273 Neutralizing antibodies are stronger .

 

 

Moderna three COVID-19 mRNA vaccines immunized mice data
Serum antigen profile of immunized 129S2 mice

 

 

 

Vaccine protective effect


After immunizing 129S2 mice for 3 weeks, the researchers conducted a challenge to determine the immune protection effect of the vaccine:

 

(1) Compared with the unvaccinated group, the body weight of mice in both high-dose and low-dose groups did not decrease within 4 days after challenge.

 

(2) After 4 days of challenge, the viral loads in the nasal cavity, lung and spleen of the mice were detected . The virus replication in the nasal cavity of the high-dose group was significantly inhibited, while the virus was basically undetectable in the lungs.

 

(3) For the low-dose group, compared with the unvaccinated group, the virus replication in the nasal cavity was also significantly inhibited, but a higher viral load of the Beta strain was detected in the lungs of the mice inoculated with mRNA-1273 and mRNA-1273.211. amount, even exceeding the viral load in the nasal cavity.

 

Moderna three COVID-19 mRNA vaccines immunized mice data
Vaccinated 129S2 mice were challenged to measure body weight and viral load in vital organs

 


The researchers also performed challenge experiments in K18-hACE2 mice, which are more susceptible to VOCs because they express the ACE2 receptor. In K18-hACE2 mice, the challenge VOCs in the nasal cavity of the high-dose group were significantly inhibited, and the replication of challenge VOCs was basically undetectable in the lungs. In general It is worth noting that a higher load of the Delta variant was detected in the lungs of mice vaccinated with low doses of the two vaccines , while the lungs of mice vaccinated with a low dose of mRNA-1273 also lost the immune protection effect against the Beta strain . , a higher beta strain load was detected.

 

 

K18-hACE2 mice were challenged, and nasal and lung viral loads were measured

 

 

 



Summary


Through this article, we can see that the lungs of mice inoculated with high doses of mRNA1273 and mRNA-1273.351 have very good immune protection effects against wild strains, Alpha, Beta, and Delta. After the challenge test, the lungs were basically detected. No viral replication.

In the high-dose group, the serum neutralizing antibody titers triggered by the two vaccines targeting various test VOCs were also similar. This indicates that serum neutralizing antibodies triggered by mRNA-1273 and mRNA-1273.351 have relatively good broad-spectrum .

 

What is strange is that 129S2 mice were immunized with low-dose mRNA1273.211 bivalent vaccine . After the challenge test, breakthrough infection of the Beta variant occurred in the lungs. Even at high doses, individual mice in the experimental group also had breakthroughs in the lungs. infection, indicating that although the bivalent vaccine contains Beta Spike , it does not appear to exhibit the advantages of the bivalent vaccine .

Judging from the Phase II clinical data of mRNA1273.211 recently released by Moderna, the serum neutralizing antibodies targeting various VOCs mutants triggered by using mRNA1273.211 as the third booster needle are only 2 higher than those using mRNA1273 as the third needle. times, also did not show a special advantage.

 

This article did not test the serum neutralizing antibody titers and immune protection effects triggered by the three vaccines. The reason for the elicited serum neutralizing antibody titers targeting Omicron was only 2-fold higher than the mRNA-1273 booster.

Since the recent epidemic strain of COVID-19 infection is Omicron, coupled with the unique properties of its Spike antigen , when designing a multivalent mRNA vaccine, Spike + , which can trigger relatively broad-spectrum serum neutralizing antibodies, obviously triggers strain-specific serum antibodies. Spike , may be a better choice .

 

 

 

 

 

 

Moderna three COVID-19 mRNA vaccines immunized mice data

(source:internet, reference only)


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