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As the COVID-19 pandemic continues into its second year, a number of variants have emerged, such as the delta variant, which is a highly contagious SARS-CoV-2 variant first identified in India in December 2020. The increase in transmissibility - the ability of a disease to be passed from one individual to another - is due to mutations of the viral spike protein, which allows entry into human cells. Findings of a report released this week show that vaccines that were effective against the original SARS-CoV-2 strain are less effective against the delta variant.

Viruses are small particles containing genetic material (RNA in the case of SARS-CoV-2) and a lipid capsule with protein structures on the surface. They do not contain the cellular machinery to create new viruses and depend on host cells for replication. Messenger RNA (mRNA) vaccines, such as the Pfizer-BioNTech and Moderna vaccines, work by delivering modified viral RNA encapsulated in a lipid membrane to human cells. These lipid droplets fuse with the lipid membranes of human cells in the respiratory tract and elsewhere and deliver mRNA to the inside of the cell. Once inside the cell, the vaccine mRNA directs the cell to produce more of the modified viral protein. This tricks the immune system into thinking these cells are infected and the body mounts an immune response that ultimately results in the production of antibodies that bind to the SARS-CoV-2 spike protein, preventing subsequent infection.

Reports published before the emergence of the delta variant demonstrate an efficacy of 95 percent for the Pfizer-BioNTech vaccine and 93 percent for the Moderna vaccine against the original Wuhan Hu-1 strain. Because the delta variant has a modified spike protein, it is unclear if vaccines designed for the original SARS-CoV-2 spike protein will be effective against current and future variants.

The authors analyzed data from patients of the Mayo Clinical Health System in Minnesota, Wisconsin, Arizona, Florida, and Iowa starting in January 2021, when the original SARS-CoV-2 strain was most prevalent, and ending in July 2021, when the delta variant was most prevalent. The study included more than 25,000 vaccinated participants and 25,000 unvaccinated participants matched for age, sex, race, ethnicity, state of residence, and history of prior SARS-CoV-2 testing.

The delta variant prevalence in Minnesota increased from less than one percent in May 2021 to over 70 percent in July 2021; whereas the original strain prevalence decreased from 85 percent to 13 over the same period. The researchers found that the Moderna vaccine was between 81 and 91 percent effective and the Pfizer-BioNTech vaccine was between 69 and 81 percent effective against infection with the original SARS-CoV-2 virus prior to May 2021. These vaccines were also highly effective in preventing hospitalization from infection with the original virus with the Moderna vaccine showing 81 to 97 percent efficacy and the Pfizer-BioNTech vaccine showing 73 to 93 percent efficacy. By July, the total effectiveness in preventing infection decreased to 76 percent for the Moderna vaccine and 42 percent for the Pfizer-BioNTech vaccine, indicating a loss of efficacy over time as variants became more common.

Next, the authors compared vaccine effectiveness across multiple states over the entire study period. In most states, the Moderna vaccine was twice as effective in preventing breakthrough infections than the Pfizer-BioNTech vaccine. This difference in effectiveness against breakthrough infections between the vaccines was highest in July, when the delta variant was most prevalent. This was especially true in Florida, where the risk of breakthrough infection was 60 percent lower after vaccination with the Moderna vaccine compared to the Pfizer-BioNTech vaccine. Across all dates, the Moderna vaccine was twice as effective in preventing COVID-19 associated hospitalization compared to the Pfizer-BioNTech vaccine.

While both vaccines demonstrate effectiveness in preventing infection and hospitalization, their effectiveness has declined over time as the prevalence of SARS-CoV-2 variants increased. The authors suggested additional studies in large and diverse populations are needed to guide public health policy. This manuscript has yet to be peer-reviewed.

Previous infection with the original strain of the SARS-CoV-2 along with vaccination creates what is known as “hybrid immunity.” People who have hybrid immunity have a broader and more robust antibody response, as observed in this trial, which is covered in this edition of the Science Digest.

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