The investigators created a panel of pseudotype viruses, which combined the HIV virus and SARS-CoV-2 spike protein.
Pfizer’s COVID-19 vaccine can protect against several emerging SARS-CoV-2 variants, according to a study published in mBio. Additionally, however, the study found that the only approved monoclonal antibody therapy for SARS-CoV-2 may not be as effective against its’ variants in laboratory experiments.
In order to conduct this research, the investigators created a panel of pseudotype viruses— replication-defective viral particles formed with a structural and enzymatic core from one virus and the envelope glycoprotein of another—which combined the HIV virus and SARS-CoV-2 spike protein. Pseudotype viruses have proven useful as research tools and carry little associated risk.
“The SARS-CoV-2 spike protein is important, because it is the only structure on the virus that is exposed to the outside. The spike protein is what sticks out from the virus; it is what the immune system recognizes and what allows the virus to stick onto target cells,” said Nathaniel Landau, PhD, professor in the Department of Microbiology at the NYU Grossman School of Medicine, in a press release.
The researchers selected HIV for their chimeric viruses for 2 reasons: first, HIV will accept almost any virus spike protein; and second, the HIV virus has been engineered to carry 2 reporter genes, which allow them to study virus entry, antibody binding, and antibody neutralization.
“The spike protein-pseudotyped lentiviruses are extremely useful experimental tools. They were developed in the course of HIV research. They are less biohazardous and easier to work with in the lab,” Landau said.
The investigators created a pseudotype virus panel using spike proteins from 6 different SARS-CoV-2 variants, which they then mixed with serum from individuals who had received the Pfizer SARS CoV-2 vaccine or who had already had COVID-19. The investigators found that convalescent sera neutralize pseudotyped viruses with the 6 variants, with only a small loss in titer. Further, according to the results of the study, the Pfizer BNT162b2 vaccination worked just as well against the majority of variants as the earlier virus, with the exception of the South African variant and the Brazil variant, which were eliminated with a 3-fold decrease in titer. That decrease is attributable to the mutation E484K, according to the study authors.
“Our interpretation of the results is that the vaccine antibodies are very powerful, and even if you lose 3-fold of the titer, there is still plenty of antibody there to neutralize the virus. We believe the findings demonstrate that the vaccines will remain protective against the variants that we tested,” Landau said in the release. “While it's not reported in this paper, we have done the same experiments with the Moderna vaccine and got similar results.”
A separate experiment tested Regeneron Pharmaceuticals’ REGN-COV2, a 2 recombinant monoclonal antibody combination of casirivamab and imdevimab. This combination has been effective in reducing symptoms in individuals with COVID-19 and keeping them from being admitted to the intensive care unit. The investigators found that casirivamab had lost some of its neutralizing activity against the South African and Brazilian variants, and the combination therapy was decreased in titer by 9 to 15 times.
“One of the Regeneron antibodies is affected by the E484K mutation, and as a result the cocktail loses some of its neutralizing activity,” Landau said. “The question with this work is 'how do the laboratory findings translate into clinical effects, that is, what will happen when you treat a patient infected with one of the variants?' We cannot say for sure. We will only know when the clinical data comes in.”
Pfizer COVID-19 vaccine protective against SARS-CoV-2 variants [news release]. EurekAlert; June 10, 2021. Accessed June 14, 2021. https://www.eurekalert.org/pub_releases/2021-06/asfm-pcv061021.php