A closer look at vaccine development

From research to reality

By Jennifer Tidball

This video shows how K-State's new Biologics Development Module will expand the university's vaccine research capabilities. Read more about the Biologics Development Module.

 

The research started a long time ago.

Long before you went into your neighborhood pharmacy to get a vaccine — whether an annual flu shot, COVID-19 booster or a shot to protect against another illness or disease. Long before a livestock producer vaccinated an entire herd or flock against an emerging disease.

That simple shot for a human or an animal is not so simple. It involved years of research and step-by-step development from an idea to the laboratory to tests and clinical trials before a thorough regulatory approval process that allowed the production and distribution of the vaccine.

“As we have seen from the COVID-19 pandemic, when available, vaccines can play an important role in protecting people from infections and for controlling the spread of viruses,” said Stephen Higgs, director of the Kansas State University Biosecurity Research Institute, or BRI.

Vaccines truly are critical, and K-State is becoming a leader for their development. From the existing biosafety level-3 laboratories at the BRI to the new Biologics Development Module that will expand vaccine research capabilities, the university is enhancing its capacity for this important line of work.

K-State scientists are studying and developing multiple human and animal vaccines and have achieved success with international collaborations, patented intellectual property and partnerships with industry. Their work will expand with nearby partners, too, including the National Bio and Agro-Defense Facility, or NBAF, as well as Scorpion Biological Services Inc. and its planned biodefense-focused biomanufacturing facility in the Manhattan area.

Read on for a closer look at several animal and human vaccine-related success stories that involve K-State research.

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Step by Step

 

Stopping swine fevers

One of the most devastating diseases for pork producers around the world is classical swine fever.

The pathogen does not affect humans, but it is an incredibly contagious swine disease. While not currently in the U.S., the virus is present in South America and has seen a resurgence in Asia, particularly China and Japan, in recent years.

“If the virus was introduced into the U.S., it would be devastating for the industry,” said Jishu Shi, the Dr. Wayne and Hilda Appleton professor of vaccine immunology in the College of Veterinary Medicine.

Shi wants to prevent that from happening by developing better vaccines for swine diseases, particularly classical swine fever and African swine fever.

His team has developed a safe and efficacious protein vaccine to protect swine against classical swine fever. They also developed a novel adjuvant — a vaccine component — that makes the immune response in swine even more effective.

The research was first licensed to an animal health company in 2018 and K-State Innovation Partners coordinated a new licensing agreement last year to use the classical swine fever vaccine platform in combination with other vaccines.

“The Biosecurity Research Institute gives us the capability to study this type of virus,” said Shi, also a Vanier and Krause BRI fellow. “This facility is unique and invaluable, and a treasure for the university and for Kansas.”

Shi’s research has received support from the NBAF Transition Fund, the Department of Homeland Security, the U.S. Department of Agriculture and animal health industry partners. His research team in the anatomy and physiology department includes Rachel Madera, senior research scientist; Lihua Wang, research assistant professor; Yuzhen Li, research associate; Amanda Rezac, research technician; and Aidan Craig, research technician.

Understanding BAPC and CAPC

A K-State-developed nanotechnology is improving vaccine effectiveness through a commercial partnership with Olathe-based Phoreus Biotechnology Inc.

John Tomich, professor of biochemistry and molecular biophysics in the College of Arts and Sciences, led an interdisciplinary research team that created the nanotechnology. They patented and licensed it to Phoreus through K-State Innovation Partners.

The research involves two technology platforms: Branched Amphiphilic Peptide Capsules, or BAPC, and Corralling Amphipathic Peptide Colloids, or CAPC. Both BAPC and CAPC are novel, nanoscale, peptide-based platforms that can increase the efficacy of vaccines and different therapies.

BAPC can be stable for extended periods at room temperature, which makes them a better delivery platform for mRNA and plasmid DNA vaccines. CAPC can deliver small drugs.

“BAPC are easy to prepare, stabilize the nucleic acids and are biodegradable. They can even be prepared dry for long-term storage,” Tomich said. “CAPC could revolutionize the small molecule drug industry since many human drugs in the development pipeline fail due to insolubility. The CAPC technology could rescue many of these drug candidates that are currently being abandoned.”

Tomich and the Phoreus team continue to collaborate with other universities and industry on using BAPC technology for vaccine development, including work related to an mRNA COVID-19 vaccine and several animal vaccines for swine and poultry.

“There is a push from many directions to build on the success of the existing mRNA COVID vaccines to expand into additional infectious diseases for both human and animal application,” said Michael Coe, chief scientific officer at Phoreus. “However, the next generation of mRNA vaccines are self-amplifying mRNA vaccines that mimic modified live virus vaccines, allowing for single-dose administration. Phoreus expects to be a leader in this new development with its BAPC technology.”

Improving COVID-19 vaccines

K-State scientists continue work on COVID-19 vaccines through an ongoing research partnership with Tonix Pharmaceuticals. K-State Innovation Partners has coordinated an option-to-license agreement and research collaboration between the two organizations.

The K-State researchers in the College of Veterinary Medicine are working to make mRNA vaccines more stable during transport and storage. This includes mRNA vaccines used against COVID-19.

“Our collaborative team is working to fast-track the stabilized formulation into preclinical models,” said Robert DeLong, associate professor at the Nanotechnology Innovation Center of Kansas State.

DeLong is leading the vaccine research, along with colleagues Waithaka Mwangi, professor of diagnostic medicine and pathobiology, and Jürgen A. Richt, director of the Center of Excellence for Emerging and Zoonotic Animal Diseases and the Center on Emerging and Zoonotic Infectious Diseases.

The collaborative team is developing a zinc particle, or ZNP, mRNA vaccine that can replace the lipid nanoparticle, or LNP, technology in current COVID-19 vaccines.

“The ZNP technology invented and developed by scientists at K-State has the potential to make mRNA vaccines that are free from LNPs, which could improve the stability of mRNA vaccines at room temperature and facilitate their deployment in places without ultra-cold chain supply systems,” said Seth Lederman, chief executive officer of Tonix.

Preventing a common cattle disease

Bovine anaplasmosis is a tick-borne disease that affects beef and dairy production in almost all U.S. states.

There is currently no effective vaccine on the market against the disease, but Roman Ganta and researchers in the College of Veterinary Medicine are changing that.

Ganta, university distinguished professor of diagnostic medicine and pathobiology, and his team with the Center of Excellence for Vector-Borne Diseases are developing a vaccine to protect cattle against bovine anaplasmosis. They have worked with K-State Innovation Partners to file a patent for their novel molecular method.

“We started this project because bovine anaplasmosis is an important cattle disease that causes billions of dollars of losses to the cattle industry in the U.S. and many parts of the world,” said Ganta, center director.

The disease is transmitted by more than 20 different tick species, which makes it one of the most prevalent tick-transmitted cattle diseases. It can also be transmitted mechanically among cows, but the disease does not affect humans.

The disease is common in nearly all of the U.S. Recent research by Ganta and his collaborators showed that about 50-60% of all beef and dairy cattle from California, Kansas and Missouri tested positive for the disease.

Their vaccine research is also important because many farmers control the disease burden by using antibiotics as a food supplement.

“The antibiotic use can also cause the development of antibiotic-resistant bacteria in addition to the unnecessary use of antibiotics to food animals,” Ganta said. “While farm practices may help control the disease, the best option is having a good vaccine.”

Ganta and his team continue to extend the vaccine’s value for field applications. They have recently published their work in PLOS Pathogens.

Other vaccine success

The vaccine success doesn’t stop there. K-State researchers are involved in numerous vaccine development projects through collaborations with other universities, organizations and industry partners.

Zika virus

Scientists with the K-State Biosecurity Research Institute, or BRI, have been involved in a large multi-institutional project to test the very first mRNA vaccine, which was first developed for Zika virus. The mRNA vaccine technology was later used for several COVID-19 vaccines.

The team published a study on the mRNA vaccine in 2017 and in 2022 the 35 co-authors received the international BIAL Award in Biomedicine, which recognizes the most important research reports in the last 20 years in biomedicine.

The College of Veterinary Medicine scientists involved include Stephen Higgs, BRI director; Dana Vanlandingham, professor of arbovirology; and Yan-Jang “Scott” Huang, research assistant professor of arbovirology.

Coronavirus in zoo animals

The K-State Center of Excellence for Emerging and Zoonotic Animal Diseases, or CEEZAD, is helping protect more than 100 mammalian species of animals in zoos around the world against infection with SARS-CoV-2, which is the virus that causes COVID-19.

Zoo animals are receiving an experimental COVID-19 animal vaccine developed by leading animal health company Zoetis. The K-State CEEZAD team, led by Jürgen A. Richt, Regents distinguished professor in the diagnostic medicine and pathobiology department, has been involved in testing the vaccine for safety and efficacy against SARS-CoV-2 infection.

Epizootic hemorrhagic

K-State researchers developed a subunit vaccine technology against epizootic hemorrhagic disease. The disease negatively affects the deer and cattle farming industry because it causes high mortality mainly in white-tailed deer and other ruminants, including cattle.

Through K-State Innovation Partners, the patented technology has been licensed to Texas-based BioStone Animal Health LLC.

The work involves multiple K-State CEEZAD researchers, including Richt, CEEZAD director; Igor Morozov, research manager; and Sun Young Sunwoo, postdoctoral fellow. William Wilson, adjunct K-State faculty member and research microbiologist with the U.S. Department of Agriculture Agricultural Research Service, also was involved.

Avian influenza

Richt also has collaborated with researchers at the Icahn School of Medicine at Mount Sinai to develop an avian influenza vaccine that has been licensed to Avimex. The vaccine is being used in Mexico.