From Chaos To Cure: Deadly Virus Structures Point Toward New Antibodies and Vaccine Targets

by François Dupont
4 comments
Lassa virus

New Antibodies and Vaccine Targets Found in Deadly Virus Structures

Scientists at Scripps Research have made significant progress in the fight against Lassa virus, a deadly pathogen prevalent in West Africa. Lassa virus causes Lassa fever, a severe illness that can lead to long-term side effects or even death. Currently, there are no widely approved treatments or vaccines for the disease. However, the recent research conducted by the Scripps Research team has identified new antibodies and vaccine targets by analyzing the structures of protein complexes from different lineages of the virus.

In their study, published in the journal Cell Reports, the researchers focused on understanding the structure of a critical protein complex that enables Lassa virus to infect human cells. By deciphering the structure, they not only gained insights into the virus’s mechanism of infection but also discovered new antibodies that bind to these proteins and neutralize the virus. This breakthrough brings hope for the development of more effective vaccines and treatments against Lassa virus.

Senior author Andrew Ward, a professor of Integrative Structural and Computational Biology at Scripps Research, emphasized the significance of this work, stating, “This work is a big step forward in our ability to isolate new antibodies to relevant sites of vulnerability on the virus, and it provides a basis to conduct rational vaccine design to broadly protect people against many lineages of the Lassa virus.”

One of the challenges in combating Lassa virus has been its genetic diversity, with various lineages exhibiting slight variations in their genes. This has made it difficult to find antibodies that can recognize all versions of the virus. Moreover, isolating the glycoproteins—spike-like proteins that surround the virus and serve as targets for antibodies—has been a struggle for scientists. The team at Scripps Research overcame these challenges by using nanoparticles to stabilize the glycoproteins into trimer complexes, which allowed them to characterize the structures of glycoproteins from different Lassa virus lineages.

Surprisingly, the researchers discovered a high level of structural similarity among the glycoproteins from distinct lineages, despite expecting more noticeable differences. This finding highlights the conservation of peptide and sugar components in the glycoproteins, which has important implications for antibody recognition and vaccine development.

To identify antibodies against the glycoprotein trimers, the researchers utilized blood samples from patients who had recovered from Lassa virus. Through this approach, they not only identified new antibodies but also studied previously discovered antibodies that recognize different lineages of the Lassa virus glycoprotein. These findings hold promise for the development of treatments and preventive vaccines against the virus.

The team at Scripps Research plans to conduct further experiments to isolate more antibodies targeting Lassa virus glycoproteins and explore potential drug targets within the protein structures. By sharing their protocols and resources, the researchers aim to contribute to the advancement of the scientific community working on Lassa virus.

The study, titled “Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies,” was authored by Hailee R. Perrett, Philip J.M. Brouwer, Jonathan Hurtado, Grace Gibson, Terrence Messmer, Aleksandar Antanasijević, Bryan Briney, and other researchers from various institutions.

Funding for this research was provided by a David C. Fairchild Endowed Fellowship, the Achievement Rewards for College Scientists Foundation, the National Institutes of Health, the Netherlands Organisation for Scientific Research, the amfAR Mathilde Krim Fellowship in Biomedical Research, the Fondation Dormeur in Vaduz, the Deutsche Forschungsgemeinschaft, the International AIDS Vaccine Initiative, and the Bill and Melinda Gates Foundation.

Frequently Asked Questions (FAQs) about Lassa virus, antibodies, vaccine targets

What is Lassa virus and why is it a concern?

Lassa virus is a dangerous pathogen prevalent in West Africa. It causes Lassa fever, which can lead to severe illness, long-term side effects, or even death. The virus infects hundreds of thousands of people every year, making it a significant concern for public health in the region.

What is the significance of the research conducted by Scripps Research?

The research conducted by Scripps Research is significant because it identified new antibodies and vaccine targets for Lassa virus. By analyzing the structures of protein complexes from different lineages of the virus, the researchers gained valuable insights into the virus’s mechanism of infection. This knowledge can contribute to the development of more effective vaccines and treatments against Lassa virus.

Why is it challenging to find antibodies that recognize all versions of Lassa virus?

Finding antibodies that can recognize all versions of Lassa virus is challenging due to the genetic diversity of the virus. Lassa virus exists in various lineages, each with slight genetic variations. These differences make it difficult to find antibodies that can effectively target and neutralize all the different strains of the virus.

How did the researchers overcome the challenges in isolating glycoproteins from Lassa virus?

The researchers at Scripps Research used nanoparticles to stabilize glycoproteins into trimers, which are the spike-like proteins that surround the Lassa virus. This technique allowed them to isolate and analyze the glycoprotein structures from different lineages of the virus. By successfully stabilizing the glycoproteins, the researchers could study their structures and identify potential targets for antibodies and vaccines.

What are the next steps in this research?

The researchers plan to conduct further experiments to isolate more antibodies against Lassa virus glycoproteins. They also intend to analyze the protein structures in more detail to identify specific sites that can be targeted with drugs. Additionally, they aim to share their protocols and resources to facilitate progress in the field and contribute to the broader scientific understanding of Lassa virus.

More about Lassa virus, antibodies, vaccine targets

  • Scripps Research: Website
  • Cell Reports Journal: Article
  • National Institutes of Health: Website
  • University of Southampton: Website
  • University of Georgia: Website
  • Philipps-University Marburg: Website
  • Amsterdam University: Website
  • Tulane University: Website
  • Netherlands Organisation for Scientific Research: Website
  • amfAR (The Foundation for AIDS Research): Website
  • Deutsche Forschungsgemeinschaft (DFG): Website
  • International AIDS Vaccine Initiative: Website
  • Bill and Melinda Gates Foundation: Website

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4 comments

Layla85 June 7, 2023 - 10:51 am

Wow, dis tex tells us abot researchers findin’ new antibodies fo’ Lassa virus. It’s so important cuz Lassa fever is a big problem in West Africa. Gud job, scientists!

Reply
JohnSmith123 June 7, 2023 - 10:51 am

Dang, I never knew dat Lassa virus could be so dangerous. But dis research is bringin’ us closer to findin’ a cure and makin’ effective vaccines. Keep up da gud work, Scripps Research team!

Reply
ScienceGeek42 June 7, 2023 - 10:51 am

The study’s findings ’bout da structural similarity in da glycoproteins is fascinatin’. It’s interestin’ how such small differences can make it hard to find antibodies. Lookin’ forward to seein’ more progress in da fight against Lassa virus!

Reply
CuriousCat June 7, 2023 - 10:51 am

I’m impressed by da researchers usin’ nanoparticles to stabilize da glycoproteins into trimers. Dat’s some next-level science right there! Hope dis leads to better treatments and vaccines soon.

Reply

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