In a groundbreaking new study, researchers from the La Jolla Institute for Immunology (LJI) have uncovered how certain human antibodies can continue to fight against the SARS-CoV-2 virus, despite its mutations. The researchers utilized samples from an anonymous San Diego resident, who has become a fascinating example of the human immune system’s ability to adapt and combat the virus.
The research not only reveals the potential of the original Moderna SARS-CoV-2 vaccine in generating antibodies against later Omicron variants, but also offers detailed 3D structures of three promising neutralizing antibodies bound to the Spike protein.
“To blunt the next pandemic and protect people from seasonal re-emergence of this one, we need antibodies of the broadest possible capacity – ones that are not escaped. We found those in a vaccinated San Diegan,” explained Dr. Erica Ollmann Saphire, CEO of LJI.
“Studying that person’s immune response in detail uncovered antibodies that are still effective against many Omicron variants,” said co-author Dr. Kathryn Hastie. “We now have to figure out how to boost these antibodies that we want over others that are less effective.”
The study, published in the journal Cell Reports, focused on a volunteer who had received two doses of the Moderna SARS-CoV-2 vaccine, with samples collected before the emergence of the Omicron variant.
The researchers then tested these samples against various variants, discovering that the volunteer maintained moderate to high levels of antibodies effective against Beta, Delta, and Omicron lineages BA.1, BA.1.1, and BA.2. Among these, they identified five antibodies capable of decreasing the infectivity of BA.1 by more than 85 percent. The team used cryo-electron microscopy to map out the vulnerabilities on the Spike protein.
“This structural work lets us see exactly how the antibodies interact with the protein and how they can neutralize the virus,” said study co-author Xiaoying Yu.
The research showed that two of the promising antibodies latch onto two parts of the protein, locking it in place to halt infection.
Results from a mouse model were also encouraging, with each of the three promising antibodies reducing the viral load in the lungs of mice infected with SARS-CoV-2 BA.1 and BA.2. The researchers plan to run more human antibodies through this same pipeline at LJI, which includes antibody isolation, screening, structural analysis, and animal model experiments.
“This research will help us combat the variants we have right now and give us targets for future vaccine development and therapeutics,” said Yu.
Coronavirus variants are different forms of the SARS-CoV-2 virus that have undergone genetic changes or mutations. As viruses replicate, they can accumulate changes in their genetic code, leading to new variants.
Some of these changes may have little impact on the virus’s behavior, while others can lead to significant differences in transmissibility, severity, or the effectiveness of vaccines and treatments.
The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) closely monitor SARS-CoV-2 variants to assess their potential impact on public health.
Key SARS-CoV-2 variants that have emerged throughout the pandemic include:
First identified in the United Kingdom in September 2020, the Alpha variant was found to be more transmissible than previous strains. This variant had a higher rate of infection and led to a rapid increase in COVID-19 cases worldwide.
First detected in South Africa in December 2020, the Beta variant also exhibited increased transmissibility. Additionally, it raised concerns due to its potential to evade immunity induced by previous infections or vaccinations to some extent.
First identified in Brazil in January 2021, the Gamma variant showed increased transmissibility and potential resistance to immunity from previous infections or vaccinations.
First discovered in India in December 2020, the Delta variant rapidly became the dominant strain globally. It displayed much higher transmissibility than previous strains, leading to surges in cases and hospitalizations. Vaccines have generally proven to be effective against severe disease caused by the Delta variant, although breakthrough infections can still occur.
First reported in South Africa in November 2021, the Omicron variant has several mutations on the Spike protein, which raised concerns about increased transmissibility, potential immune evasion, and the effectiveness of vaccines. Early data suggest that while vaccines may be less effective in preventing Omicron infections, they still provide protection against severe disease and hospitalization.
Scientists continue to study these and other emerging SARS-CoV-2 variants to better understand their characteristics and devise appropriate public health strategies. Vaccination, along with other preventive measures such as masking, social distancing, and good hand hygiene, remains a crucial tool in combating the virus and its variants.