New vaccine could protect against variants of coronavirus and similar viruses

  • Researchers recently developed a new vaccine candidate named Mosaic-8 that could protect against both SARS-CoV-2 variants and other closely related coronaviruses that could cause outbreaks in the future.
  • The researchers found that mice and non-human primate models immunized with Mosaic-8 produced a broadly neutralizing antibody response against SARS-CoV-2 variants and related coronaviruses.
  • The mosaic-8 vaccine also conferred protection against severe disease due to SARS-CoV-2 variants and SARS-CoV-1 in these animal models.
  • This new vaccine could eliminate the need to update the vaccine with the emergence of new variants of SARS-CoV-2 or an outbreak due to a closely related coronavirus.

A recent study published in the journal Science shows that mosaic-8, a nanoparticle-based vaccine candidate, could confer broad protection against concerning variants of SARS-CoV-2 and other related coronaviruses.

Study co-author Dr Pamela J. Bjorkman, a professor at the California Institute of Technology, said: “SARS-CoV-2 has been shown to be capable of manufacturing many new variants that have prolonged the global pandemic. of COVID-19. Additionally, the fact that three betacoronaviruses – SARS-CoV, MERS-CoV, and SARS-CoV-2 – have spread to humans from animal hosts over the past 20 years illustrates the need to manufacture vaccines. largely protective.

Dr Bjorkman added that it is not possible to predict which virus among the large number found in animals will evolve in the future to infect humans and cause another epidemic or pandemic.

“What we are trying to do is make an all-in-one vaccine that is protective against SARS-like betacoronaviruses, regardless of which animal viruses might evolve to allow human infection and spread. This type of vaccine would also protect against current and future variants of SARS-CoV-2 without requiring an update,” Dr. Bjorkman said.

The emergence of new variants of SARS-CoV-2 has prolonged the COVID-19 pandemic. COVID-19 vaccines approved so far were developed to target wild-type SARS-CoV-2 spike protein.

A large number of mutations in the Omicron variant spike protein has diminished the ability of existing COVID-19 vaccines to prevent breakthrough infections. Thus, COVID-19 vaccines are currently being updated to increase their effectiveness against potential new variants of concern.

SARS-CoV-2 belongs to the genus sarbecovirus, which also includes other similar viruses. For example, SARS-CoV-1, the virus responsible for the severe acute respiratory syndrome (SARS) outbreak in 2003, is also part of the sarbecovirus.

Additionally, a number of sarbecoviruses have been found in bats, some able to bind to the same receptor on human cells as SARS-CoV-2 and SARS-CoV-1. Thus, it is possible that another sarbecovirus jumps from an animal species to humans and causes a new epidemic or pandemic.

This highlights the need for a vaccine that could confer protection against new variants of SARS-CoV-2 and other sarbecoviruses.

The spike protein expressed on the surface of SARS-CoV-2 plays an important role in mediating virus entry into human cells. More specifically, the receptor binding domain (RBD) of the spike protein interacts with angiotensin-converting enzyme 2 (ACE2) receptors expressed by nearly all human tissues, facilitating virus entry into human cells.

Immunization with a COVID-19 vaccine generates an immune response against the wild-type SARS-CoV-2 spike protein RBD. This immune response includes neutralizing antibodies that bind to the RBD and prevent the spike protein from interacting with ACE2 receptors, thereby inhibiting infection of human cells.

These neutralizing antibodies primarily bind to two subregions of the RBD. However, these subregions of the RBD spike protein are prone to mutations, with their sequences showing considerable variation among SARS-CoV-2 variants.

This explains the decreased neutralizing antibody response against SARS-CoV-2 variants after vaccination. Moreover, these subregions of the RBD spike protein exhibit a high degree of sequence variability among different sarbecoviruses.

The authors of the present study had previously discovered two other RBD subregions that are conserved among these sarbecoviruses. Additionally, fewer mutations are seen in these subregions in SARS-CoV-2 variants of concern.

Researchers have now developed a vaccine that elicits an immune response against these conserved subregions of the RBD spike protein. This vaccine, called Mosaic-8, includes an RBD spike protein from SARS-CoV-2 and seven other related sarbecoviruses that are chemically attached to a protein nanoparticle.

The presence of RBDs from eight different sarbecoviruses teaches the immune system to mount a response against a wide range of proteins. The use of protein fragments that are more likely to be conserved across sarbecoviruses suggests that this vaccine could also identify sarbecovirus RBDs that were not present on the nanoparticle.

In other words, the mosaic-8 vaccine could produce a cross-reactive antibody response against a wide range of sarbecoviruses. Such a vaccine could potentially eliminate the need to update the vaccine with the emergence of new variants or sarbecoviruses that jump from animals to cause disease in humans.

In the current study, researchers evaluated the ability of the Mosaic-8 vaccine to elicit an immune response in a mouse model and rhesus macaques.

Since mice are relatively resistant to SARS-CoV-2 infection, the researchers used genetically modified mice that express the human ACE2 receptor to make them susceptible to SARS-CoV-2 infection.

These mice were immunized with the Mosaic-8 vaccine or homotypic SARS-CoV-2 RBD nanoparticles, which were conjugated with only the SARS-CoV-2 RBD instead of 8 different RBD fragments.

Immunization with mosaic-8 vaccine resulted in lower serum neutralizing antibody levels against SARS-CoV-2 variants than homotypic SARS-CoV-2 RBD nanoparticles. Notably, vaccination with the mosaic-8 vaccine resulted in higher neutralizing antibody titers against SARS-CoV-1 and other sarbecovirus spike proteins. Similarly, rhesus macaques immunized with mosaic-8 also showed a strong neutralizing antibody response against worrisome variants of SARS-CoV-2 and other sarbecoviruses.

Although the RBDs of sarbecoviruses such as SARS-CoV-1 were not included in the mosaic-8 vaccine, immunization with this nanoparticle vaccine resulted in a strong neutralizing antibody response against these viruses. In other words, use of the conserved RBD subregions on the Mosaic-8 vaccine potentially resulted in cross-reactivity against a range of sarbecoviruses.

To compare the ability of this nanoparticle-based vaccine to protect against severe disease, mice previously immunized with the Mosaic-8 vaccine, homotypic SARS-CoV-2 RBD nanoparticles, or unconjugated nanoparticles were infected with SARS- CoV-2 or SARS-CoV-1.

Mice infected with SARS-CoV-2 tend to lose weight after the onset of infection. Consistent with this, infection with either virus resulted in significant weight loss and death in the control group injected with unconjugated nanoparticles.

Mice immunized with mosaic-8 nanoparticles did not show weight loss after infection with SARS-CoV-1 or SARS-CoV-2. The mosaic-8 vaccine also suppressed viral replication in the lungs and upper respiratory tract and protected mice from death after infection with either virus.

Similar experiments in rhesus macaques showed that immunization with the Mosaic-8 vaccine protected against both the SARS-CoV-2 Delta variant and against SARS-CoV-1. In other words, the mosaic-8 vaccine conferred protection against the concerning variants of SARS-CoV-1 and SARS-CoV-2.

Homotypic SARS-CoV-2 RBD nanoparticles exerted protective effects against SARS-CoV-2 infection in mice, but not against SARS-CoV-1 infection. This further demonstrates the use of RBDs from 8 different sarbecoviruses protected not only against SARS-CoV-2 variants, but also against other related viruses not shown on the mosaic-8 nanoparticles.

The researchers will conduct phase 1 clinical trials to examine whether these results obtained with Mosaic-8 in animal models can be reproduced in humans.

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