Moderna’s COVID-19 vaccine elicits a 6-month antibody response to mutants

Researchers in the United States are Coronavirus Disease 2019 (COVID-19).

“Most mRNA-1273 vaccinated individuals maintained binding and functional antibodies to the SARS-CoV-2 mutant for 6 months,” they write.

The team comprehensively assesses the impact of the B.1.1.7 variant (appearing in the UK) and B.1.351 (South Africa), P.1 (Brazil), B.1.429 (California), and B.1.526 (new). Did. The York) mutant had vaccine-induced binding, neutralization, and angiotensin converting enzyme 2 (ACE2) blocking antibodies for 7 months. The ACE2 receptor is the host cell structure to which SARS-CoV-2 attaches as an early step in the infectious process.

Researchers report that a single dose of the mRNA-1273 vaccine rarely causes a cross-reactive neutralization reaction.

However, when the response to the second dose peaked, all participants showed strong antibody activity against all mutants.

In addition, neutralizing antibody activity against the SARS-CoV-2 mutant persisted for 6 months after the second dose, although the level was reduced compared to the activity against the original Wuhan-1 strain.

Overall, the B.1.351 variant had the greatest effect on antibody recognition, while the B.1.1.7 variant had the least.

Researchers say the findings support the use of vaccines to protect against mutants and complement ongoing clinical protection studies to signal the potential need for additional booster immunization. I have.

The study was conducted by Nicole Doria Rose and colleagues at the National Institutes of Health in Bethesda, Maryland, researchers at Emory University School of Medicine in Atlanta, Georgia, Emmes Company in Rockville, Maryland, and Moderna in Cambridge, Massachusetts. It was carried out. Kaiser Permanente Washington Institute of Health in Seattle.

The preprinted version of the research treatise is bioRxiv* Servers and articles have been peer reviewed.

Mutants of concern have been shown to avoid antibody neutralization

Since the first COVID-19 pandemic began in late December 2019, SARS-CoV-2 Concerned Mutant Strains (VOCs) have emerged that show resistance to neutralizing antibody activity induced by spontaneous infection or vaccination.

By the summer of 2020, the original first Wuhan-Hu-1 (WA1) strain had been replaced with a B.1 variant containing the virus mutant D614G. Spike protein.. Spikes are the main structure that viruses use to infect host cells. Neutralizing antibody..

Since then, other varieties have emerged that have been shown to show increased transmission rates.

The first variants that caught the world’s attention were the B.1.1.7 strain that emerged in the United Kingdom and the B.1.351 variant that emerged in South Africa. These VOCs contain 8 or 9 mutations in the peplomer protein that were not present in the original WA1 strain.

Importantly, the B.1.351 mutant has been shown to be up to 15-fold more resistant to antibody neutralization by serum from individuals vaccinated with WA1-based vaccines.

More recently, VOC P.1 (Brazil) and B.1.429 (California) and Variant of Interest B.1.526 (New York) have moderate resistance to serum neutralization from convalescent individuals and vaccinated individuals. Is shown to indicate.

“These previous studies evaluated vaccine sera of individuals who were vaccinated only immediately after the first or second dose of various vaccines. Similarly, clinical studies evaluated B.1.1.7 and Efficacy and efficacy against B.1.351 variants have been reported, but these are in the first few months after vaccination, “says Doria-Rose et al.

The team states that such data provide important insights into the performance of vaccines against these viral variants, but do not address cross-reactive binding and durability of functional antibodies.

What did the researchers do?

Researchers used SARS-CoV-2, an ACE2 blocking assay Pseudovirus Neutralization assay and live virus neutralization to measure the functional properties of the mRNA-1273-induced antibody response to B.1.1.7, B.1.351, P.1, B.1.429, and B.1.526 variants over time. Assay.

Serum samples were taken from individuals who received 100 mcg of vaccine twice (every 28 days) and were followed up for 7 months after the first dose.

What did the study find?

Cross-reactive antibody neutralizing reactions to mutants were rare after a single dose of mRNA-1273.

“Observation of the limited size and breadth of neutralizing activity on day 29 underscores the importance of a complete double-dose regimen of the mRNA vaccine for protection against SARS-CoV-2 mutants.” The team is writing.

However, two weeks after the second dose, all participants showed strong antibody responses to all mutants.

“Importantly, all subjects showed widespread cross-reactivity activity against all mutants on day 43, the peak of the response,” the researchers said.

In addition, binding and functional antibodies to the mutant persisted in most individuals for 6 months after the second vaccination, albeit at low levels.

Neutralization of D614G and mutant pseudovirus lasts for 6 months. 100 ug of mRNA-1273 was delivered on days 1 and 29. Each line represents pseudovirus neutralization ID 50 on days 29 (4 weeks after the first dose), day 43 (2 weeks after the second dose), 119, and 209 days of one subject. N = 8 per group. False serum neutralizing activity of subjects aged 18-55 (upper), 56-70 (middle), 71 years and older (lower) with spikes of D614G (left) and B.1.1.7 (middle) Measured against viruses. , Or B.1.351 (right).

B.1.351 mutant was most resistant to antibody targeting

All assays showed that the mutations present in B.1.1.7 had minimal effect on antibody recognition and function. In contrast, the B.1.351 mutation had a significant effect in the 3- to 15-fold range, depending on the assay. Variants P.1, B.1.429, and B.1.526 variants showed intermediate effects.

However, the team states that although antibody activity against the most resistant mutant, B.1.351, declined significantly over time, it was not completely nullified. On day 209, 58% of the serum showed detectable and potent neutralizing activity against B.1.351 in the pseudoviral assay, similar to 63% in the live virus assay.

In addition, all individuals retain binding activity and 79% may block the binding of ACE2 to RBD with B.1.351.

What did the team conclude?

“In summary, mRNA-1273-induced neutralizing antibody activity against SARS-CoV-2 mutants persisted for 6 months after the second dose, although levels were reduced compared to WA1.” Rose et al. State.

“These data complement ongoing studies of clinical protection to signal the potential need for additional booster immunization,” they write.

The team says additional research is needed to address the effects of new mutants that may occur, but current findings support the use of this vaccine to protect against mutants.

*Important Notices

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.