T cell response

Scientists find out what makes people survive Ebola

Scientists conducting the first comprehensive study of key immune system cells—collected from West African Ebola survivors— have made a surprising discovery that provides important clues to developing effective vaccines against the infection.

Microscopic view of the Ebola virus

Source: Shutterstock/jaddingt

The whole idea of vaccination is to mimic the immune response that the person makes after they have the infection and get over the infection

Michael B. Oldstone

The study, which focused on immune system sentries known as killer (CD8+) T cells, showed that nearly all (96 percent) of the Ebola survivors had T cells that responded to viral protein, nucleoprotein on cells expressing Ebola proteins. In contrast, it was surprising that the virus’s outer glycoproteins, presumed to be the main targets for killer T cells, were recognized in a minority (38 percent) of previously infected individuals.

“The whole idea of vaccination is to mimic the immune response that the person makes after they have the infection and get over the infection,” says Michael B. Oldstone, MD, a professor at Scripps Research and senior author of a paper reporting the findings, published today in the journal Proceedings of the National Academy of Sciences. The research was supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. “Our study of the immune response in Ebola survivors,” Oldstone adds, “suggests that a vaccine targeting not only the glycoprotein but Ebola’s nucleoprotein would likely be more effective than the current vaccines that only express the glycoprotein.”

In collaboration with the government of Sierra Leone and research partners at Tulane University, the Massachusetts Institute of Technology and Harvard University, the researchers analyzed blood samples from 30 survivors of the 2013–2016 Ebola epidemic in West Africa. Their goal was an unbiased study designed to characterize the total cytotoxic killer T cell response to the Ebola virus proteins in these survivors. CD8+ cytotoxic T cells destroy infected cells that are the factories producing the virus.

Laboratory examination of Ebola. Scientist takes blood pipette and microscope...
Laboratory examination of Ebola

Source: Shutterstock/science photo

To study CD8+ cytotoxic T cell responses in these survivors, the researchers tested the blood samples against seven of the eight proteins encoded by the Ebola virus’s genetic material. These proteins are expressed on cells infected by Ebola virus. In the new study, the scientists cut the viral proteins into small pieces, called peptides, which complex with specialized proteins unique for each individual, termed the human leukocyte antigen (HLA). The HLA/viral peptide complex is transported from inside the infected cell to its outer surface. Once presented there, the cytotoxic T cell recognizes the complex resulting in activation and destruction of the infected cell. The HLA/peptide complex forms the “epitope” recognized by the specific CD8+ cytotoxic T cell.

The team found that 96 percent of the Ebola survivors made cytotoxic CD8+ T cells that responded to a protein of Ebola virus called the nucleoprotein. Meanwhile, only 38 percent of these survivors responded to either of the virus’s two glycoproteins. This finding came as a surprise because other studies had suggested that the glycoprotein was the main target for effective immune responses and current experimental Ebola vaccines have been designed to only contain the Ebola glycoprotein. This study also revealed 34 new, smaller sites, called epitopes, on Ebola virus proteins killer T cells specifically target. The discovery of these epitopes will inform future studies of how the immune system targets the virus.

Going forward, the researchers plan to study samples from people who may have been infected with Ebola virus but never presented with symptoms, such as the family members of victims of the epidemic. They also hope to uncover why some people survived Ebola virus infection, only to experience reactivation of the virus months or years later. “Now that we are analyzing in depth the basic T cell responses, numerous studies by us and others are to follow,” Oldstone says.


Source: Scripps Research Institute

24.07.2018

Read all latest stories

Related articles

Photo

CRISPR

Could gold be the key to making gene therapy for HIV?

A proof-of-principle study shows that gold nanoparticles loaded with CRISPR and other gene-editing tools safely and effectively edited blood stem cells.

Photo

Virology

Trapping viruses inside a cell: harmful or helpful?

Viruses are often used as vehicles for delivery in gene therapy because they’re engineered not to damage the cell once they get there, but neglecting to consider how the virus will exit the cell…

Photo

X-ray crystallography

Seeing the unseeable life inside a virus

Researchers at Cardiff University have used x-ray crystallography and computer simulation to get a closer look at how viruses bind cells and cause infection. The new insight could help in the…

Related products

Atlas Genetics - Atlas Genetics io system

Infectious diseases testing

Atlas Genetics - Atlas Genetics io system

Atlas Genetics Ltd
Beckman Coulter – Anti-Mullerian Hormone (AMH)

Immunochemistry

Beckman Coulter – Anti-Mullerian Hormone (AMH)

Beckman Coulter, Inc.
Beckman Coulter – phi (Prostate Health Index)

Immunochemistry

Beckman Coulter – phi (Prostate Health Index)

Beckman Coulter, Inc.
Beckman Coulter – Vitamin D Assay

Immunoassays

Beckman Coulter – Vitamin D Assay

Beckman Coulter, Inc.
DiaSys Diagnostic Systems - BioMajesty JCA-BM6010/C

Clinical chemistry

DiaSys Diagnostic Systems - BioMajesty JCA-BM6010/C

DiaSys Diagnostic Systems GmbH