Researchers in the United States found that Moderna’s coronavirus disease 2019 (COVID-19) vaccine is persistent against the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a study showing that it provides a protective protection. Rhesus monkey.
The delta mutant, first identified in India in October 2020, is now the predominant strain worldwide and is associated with increased infectivity and more severe COVID-19.
Effectiveness of Moderna’s mRNA-1273 for the SARS-CoV-2 delta variant has been shown to decline over time. However, there are limited data on the impact of sustained immune response on protection.
Currently, a team from the National Institute of Allergic Infectious Diseases in Bethesda, Emory University School of Medicine in Atlanta, Bioqual Inc. in Rockville, and Moderna Inc. in Cambridge are reporting on two doses of mRNA-immunized red lizard monkeys. In 1273, 48 weeks later, I challenged the Delta variant.
Robert Seder and his colleagues, with their binding force Neutralizing antibody Blood and lower respiratory tract titers in animals decreased during the 48 weeks post-vaccination.
Four days after the challenge with the delta mutant, mRNA-1273-mediated protection in the lungs was persistent, but delayed and may depend on previous antibody responses, the team said.
The findings suggest that rapid and sustained defense of the upper and lower respiratory tracts may ultimately require booster vaccines.
The preprinted version of the research paper is bioRxiv* The server while the article is being peer reviewed.
Concerns over the weakening of immunity caused by vaccines
The mRNA-based vaccine developed by Pfizer BioNTech and Moderna has been shown to provide substantial protection against vaccine-compatible early strains of SARS-CoV-2 – USA-WA1 / 2020 (WA1). ..
However, since the development of these vaccines, SARS-CoV-2 variants have emerged with mutations that confer resistance to vaccine-induced neutralization, and the protection provided by mRNA-1273 and other vaccines. Raises concerns about the sustainability of.
The Delta mutant, first identified in India in October 2020, is now the major circulating strain of SARS-CoV-2 and has been designated by the World Health Organization as a mutant of concern.
Delta contains mutations in the viral receptor binding domain (RBD) Spike protein This contributes to both increased binding to host cell receptors and reduced neutralization by vaccine-induced antibodies.
Neutralizing antibody titers in mRNA-1273 vaccinated sera have been shown to be reduced by a factor of 3 relative to delta variants compared to WA1 immediately after immunization.
However, recent studies in the United Kingdom, the United States, and Qatar show that mRNA-based vaccines appear to be one-third more protective against asymptomatic and symptomatic B.1.617.2 infections, but are severe. It has also been shown that its protective effect against the disease is not. Reduction.
“In addition, there is no analysis of mRNA-1273-induced immunity up to 1 year in the context of protection against mild and severe disease of the upper and lower respiratory tracts,” Seder et al. Write.
What did the researchers do?
The team immunized eight rhesus monkeys with 100 µg of mRNA-1273 at weeks 0 and 4 and infected the delta mutant 48 weeks later.
To assess potential protection mechanisms, researchers measured antibody titers in blood and upper and lower respiratory tracts, following both vaccination and Delta challenges. They compared the findings with eight unvaccinated (control) animals challenged in Delta at week 48.
What did the study find?
Serum neutralizing titers for delta were significantly reduced 48 weeks after vaccination, with 280 at 6 weeks and 34 reciprocal 50% inhibitory dilution (ID50) at 48 weeks.
Antibody binding titers also decreased with bronchoalveolar lavage (BAL) over the last 48 weeks.
Four days after the challenge, lower respiratory tract protection was completed. However, the virus could not be cultivated in BAL, and the subgenomic RNA (sgRNA) of the virus was reduced by about 3 logs.Ten, Compared to control animals.
B.1.617.2 S-2P-binding serum antibody recognizes epitopes associated with neutralization (A) Measured serum in which relative serum reactivity competes with a single monoclonal antibody (mAb) that targets cross-reactive RBD It was measured as the total competition rate for antibody S-2P binding. Epitopes of both WA1 and B.1.617.2S-2P 48 weeks after immunization. Antigen sites are by mAb LY-COV555 (site E), A20-29.1 (site C), S309 (site G), B1-182 (site A), CB6 (site B), and A19-61.1 (site F). It is defined. .. 5 NHP per group. B.1.617.2 Statistical analysis showing the competitive rate of binding to the indicated epitopes on WA1S-2P compared to S-2P. (BC) Longitudinal analysis of serum reactivity relative to both WA1 (B) and B.1.617.2 S-2P (C) cross-reactive RBD epitopes at 6, 24, and 48 weeks post-immunization. I evaluated it. 5-8 NHP per group. A statistical analysis is shown of the competition rate for binding to the indicated epitopes at week 48 compared to week 6. (D) B.1.617.2 mutations are shown in red and black deletions are non-neutralized (LY-COV555, S309) and neutralized (B1-182, CB6, A19-61.1) mAbs. (E) Both non-neutralized (LY-COV555, S309) and neutralized (B1-182, CB6, A19-61.1) mAb footprints are bound on the B.1.617.2 receptor binding domain (RBD). Indicates a region, mutation is red.
Importantly, an impressive history of antibody reactions was observed in the lower respiratory tract. Geometric mean titers for delta increased 590-fold by day 4 after challenge compared to pre-challenge time, and sgRNA was detected in 6 of 8 vaccinated animals by day 7. did not.
Researchers say these findings suggest that lower respiratory tract protection is durable, but somewhat delayed, and may depend on recall antibody reactions.
In nasal swabs, sgRNA was reduced by 1 logTen The virus remains incubable, suggesting that higher threshold antibodies are needed to protect the upper respiratory tract compared to the lower respiratory tract.
The team states that these data are consistent with human vaccinated studies showing that immunization can provide significantly higher levels of protection against mild or asymptomatic infections. increase.
What is the impact?
Seder et al. State that the results of this study suggest that the mRNA-1273 vaccine provides lasting protection against lower respiratory tract deltas, presumably through induction of antibody reactions in the lungs. ..
However, they add that it is important to consider both the limited control of the virus in the nose and the temporary delay in the lungs. This may provide the virus with a more important opportunity for transmission, especially when mutants that are more contagious, more toxic, and more resistant to neutralization emerge.
Researchers advise that in situations where viral control in the upper respiratory tract is restricted and control in the lower respiratory tract is slow, booster immune vaccines to increase antibody titers may ultimately be justified. doing.
bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.
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