Scientists Jump Hurdle in HIV Vaccine Design

15/06/2017

Scientists Jump Hurdle in HIV Vaccine Design LA JOLLA, CA May 26, 2017 Scientists at The Scripps Research Institute (TSRI) have made another important advance in HIV vaccine design. The development was possible thanks to previous studies at TSRI showing the structures of a protein on HIV's surface, called the envelope glycoprotein. The scientists used these structures to design a mimic of the viral protein from a different HIV subtype, subtype C, which is responsible for the majority of infections worldwide.

The new immunogen is now part of a growing library of TSRI-designed immunogens that could one day be combined in a vaccine to combat many strains of HIV.

All of this research is going toward finding combinations of immunogens to aid in protecting people against HIV infection, said TSRI Professor Ian Wilson, Hanson Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI.

The research, published recently in the journal Immunity, was led by Wilson and TSRI Professor of Immunology Richard Wyatt, who also serves as Director of Viral Immunology for the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center at TSRI.

The new study was published alongside a second study in Immunity, led by scientists at the Karolinska Institute in Stockholm, which showed that the vaccine candidate developed in the TSRI-led study can elicit neutralizing antibodies in non-human primates.

Together, the two studies reiterate how structure-based immunogen design can advance vaccine development, said Wyatt.

Solving the Clade C Structure

HIV mutates rapidly, so there are countless strains of HIV circulating around the world. Of these strains, scientists tend to focus on the most common threats, called clades A, B and C.

Like a flu vaccine, an effective HIV vaccine needs to protect against multiple strains, so researchers are designing a set of immunogens that can be given sequentially or as a cocktail to people so their immune systems can prepare for whatever strain they come up against.

In 2013, TSRI scientists, led by Wilson and TSRI Associate Professor Andrew Ward, determined the structure of a clade A envelope glycoprotein, which recognizes host cells and contains the machinery that HIV uses to fuse with cells. Because this is the only antibody target on the surface of HIV, an effective HIV vaccine will have to trigger the body to produce antibodies to neutralize the virus by blocking these activities.

Building on the previous original research, the scientists in the new study set out to solve the structure of the clade C glycoprotein and enable the immune system to fight clade C viruses.

Clade C is the most common subtype of HIV in sub-Saharan Africa and India, explained study co-first author Javier Guenaga, an IAVI collaborator working at TSRI. Clade C HIV strains are responsible for the majority of infections worldwide.

The scientists faced a big challenge: the clade C envelope glycoprotein is notoriously unstable, and the molecules are prone to falling apart.

Guenaga needed the molecules to stay together as a trimer so his co-author Fernando Garces could get a clear image of the clade C glycoprotein's trimeric structure. To solve this problem, Guenaga re-engineered the glycoprotein and strengthened the interactions between the molecules. We reinforced the structure to get the soluble molecule to assemble as it is on the viral surface, Guenaga said.

The project took patience, but it paid off. Despite all the engineering employed to produce a stable clade C protein, these crystals (of clade C protein) were grown in very challenging conditions at 4 degrees Celsius and it took the diffraction of multiple crystals to generate a complete dataset, as they showed high sensitivity to radiation damage, said Garces. Altogether, this highlights the tremendous effort made by the team in order to make available the molecular architecture of this very important immunogen.

With these efforts, the glycoprotein could then stay together in solution the same way it remains together on the virus itself. The researchers then captured a high-resolution image of the glycoprotein using a technique called x-ray crystallography.

The researchers finally had a map of the clade C glycoprotein.

Vaccine Candidate Shows Promise

In a companion study, the scientists worked with a team at the Karolinska Institute to test an immunogen based on Guenaga's findings. The immunogen was engineered to appear on the surface of a large molecule called a liposome creating a sort of viral mimic, like a mugshot of the virus.

This vaccine candidate indeed prompted the immune system to produce antibodies that neutralized the corresponding clade C HIV strain when tested in non-human primates.

That was great to see, said Guenaga. This study showed that the immunogens we made are not artificial molecules these are actually relevant for protecting against HIV in the real world.

In addition to Wyatt, Wilson and Guenaga, the study, Glycine substitution at helix-to-coil transitions facilitates the structural determination of a stabilized subtype C HIV envelope glycoprotein, included co-first author Fernando Garces, Natalia de Val, Viktoriya Dubrovskaya and Brett Higgins of TSRI; Robyn L. Stanfield of TSRI and IAVI; Barbara Carrette of IAVI; and Andrew Ward of TSRI, IAVI and the Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID) at TSRI.

This work was supported by the IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD; grants OPP1084519 and OPP1115782), CHAVI-ID (grant UM1 AI00663) and the National Institutes of Health (grants P01 HIVRAD AI104722, R56 AI084817 and U54 GM094586).

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the worlds

LINK:	http://www.scripps.edu/news/press/2017/20170526wyatt_wilson.html...
	See more stories from scripps

Most recent headlines

05/01/2027

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be demoed at CES 2026

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...

01/06/2026

Dolby Sets the New Standard for Premium Entertainment at CES 2026

January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026 Throughout the week, Dolby brings to life the latest innovatio...

02/05/2026

Dalet Flex LTS Delivers Smarter Search, Faster Editing, and an AI-Ready Foundation for Modern Media

Dalet, a leading technology and service provider for media-rich organizations, t...

01/05/2026

NBCUniversal's Peacock to Be First Streamer to Integrate Dolby's Full Suite of Premium Picture and Sound Innovations

January 5 2026, 18:30 (PST) NBCUniversal's Peacock to Be First Streamer to ...

01/04/2026

DOLBY AND DOUYIN EMPOWER THE NEXT GENERATON OF CREATORS WITH DOLBY VISION

January 4 2026, 18:00 (PST) DOLBY AND DOUYIN EMPOWER THE NEXT GENERATON OF CREATORS WITH DOLBY VISION Douyin Users Can Now Create And Share Videos With Stun...

18/03/2026

Net Insight Names Larissa GrnerMeeus CPO

Newly named chief product officer (CPO), Larissa G rner Meeus will return to Net Insight on May 4. Larissa G rner Meeus will become CPO of Net Insight on May 4...

18/03/2026

SVG Europe's The Football Summit 2026: Select Sessions Now Available to Watch on SVG PLAY

SVG Europe's The Football Summit 2026 explored how the sports broadcasting i...

18/03/2026

SVG's SportsTech@NABShow Blog Goes Live as Countdown to Vegas Heats Up

The 2026 NAB Show kicks off one month from today and SVG is once again set to cover the show from every angle. SVG's SportsTech@NAB Show Blog is now live - ...

18/03/2026

The Premiere of Dead Lover Showcases Grave Robbing and Sex With a Giant Finger

(L-R) The cast and crew of Dead Lover at The Ray Theater for its premiere at the 2025 Sundance Film Festival. (Photo by Robin Marshall/Shutterstock for Sundan...

18/03/2026

Music Row Piano from Wiltone Productions

Yamaha C7 captured in Nashville Wiltone Productions have announced the release of Music Row Piano, a deeply sampled Yamaha C7 piano library that's been ...

18/03/2026

Techivation introduce T-Warmer Mk2

Bass-enhancement plug-in upgraded Along with a steady stream of new releases, Techivation have recently been revisiting some of the older plug-ins in their ...

18/03/2026

Tonal Balance Control 3 from iZotope

Mix-reference plug-in overhauled iZotope's powerful mix-referencing plug-in has just reached its third major version, and now boasts a new capture proce...

18/03/2026

Toontrack Transistor Organ EKX

Latest EZKeys 2 expansion arrives Toontrack's staggering collection of EZKeys 2 expansions has grown once again, and the latest instalment delivers a on...

18/03/2026

Jess Ho explores the politics of food in new SBS Audio podcast For The Culture

Jess Ho explores the politics of food in new SBS Audio podcast For The Culture 18 March, 2026 Media releases New SBS Audio podcast For The Culture, hosted ...

18/03/2026

Future-ready broadcasts with ATSC 3.0 and enhanced services from Rohde & Schwarz at NAB 2026

Future-ready broadcasts with ATSC 3.0 and enhanced services from Rohde & Schwarz...

18/03/2026

LCTWS 2026

London Calling - When The Industry Convened to Help Streaming Find its MoJo In this blog, Laura Rognoni reflects on key discussions from the Connected TV World...

18/03/2026

SMPTE Unveils 2026 NAB Show Educational Presentations

SMPTE Unveils 2026 NAB Show Educational Presentations Brie Clayton March 18, 2026 0 Comments SMPTE , the home of media professionals, technologists, a...

18/03/2026

Auditel Ad Campaign Shot on Blackmagic PYXIS 12K

Auditel Ad Campaign Shot on Blackmagic PYXIS 12K Brie Clayton March 18, 2026 0 Comments LED wall virtual production blends 12K open gate acquisition w...

18/03/2026