Two Te Herenga Waka—Victoria University of Wellington immunologists are among the successful recipients of funding from the Health Research Council (HRC) of New Zealand announced yesterday.

Professor Anne La Flamme and Dr Lisa Connor from Te Kura Mātauranaga Koiora—School of Biological Sciences have received nearly $1.2 million each for their research over the next three years, as part of the HRC’s 2021 Project Grants round.

Professor La Flamme’s research will look at how brain inflammation is prevented using a novel chemical compound, designed by Dr Olga Zubkova from the University’s Te kāuru—Ferrier Research Institute, that inhibits the harm done by the enzyme heparanase. Her team’s work could ultimately lead to the development of therapeutics to prevent damage caused by immune cells in diseases such as multiple sclerosis.

“We have two key aims, one basic science aim and a second practical aim,” says Professor La Flamme.

“First, we want to understand how immune cells enter the brain during health and during neurological diseases such as multiple sclerosis, meningitis, schizophrenia, Alzheimer’s, and traumatic brain injury.

“In particular we will investigate the specific molecules in the barriers that divide the brain from the rest of the body. These barriers control the entrance of immune cells and if this control is compromised damaging brain inflammation can result.

"The second aim is to develop a therapy that targets these specific structures so we can restore normal control of immune cell migration through these barriers. Using novel chemistry, we have created a compound we can use to help develop innovative targeted therapeutics in the future.”

Dr Connor and her team are looking at how lung resident immune cells can be used to create mucosal vaccines for respiratory pathogens such as the influenza virus, which kills about 500 New Zealanders a year.

These vaccines can be delivered orally or intranasally to induce mucosal immunity, which provides a first line of defence, working quickly and potentially preventing diseases spreading to other parts of the body.

The team’s work could ultimately influence the design of the next generation of mucosal vaccines for influenza.

Dr Connor says protection against respiratory pathogens is initiated by the body’s mucosal immune system but most licensed vaccines are administered by an injection and do not induce fast-acting immunity at the site of infection.

Rigorous safety requirements mean new vaccines often require inclusion of an adjuvant, which enhances the body’s immune response.

“This poses a major barrier for mucosal delivery, as most adjuvant formulations are not suitable. Our research focuses on a novel class of adjuvants that harness resident innate-like T cells. Importantly, we have generated evidence to show that when these adjuvants are co-administered with an antigen they induce potent antibody responses.”

The goal of the project is to identify the key immune cells and molecular events involved in driving the immune response, which in turn will inform the formulation and structural design of an optimal mucosal vaccine for influenza.

Dr Connor says using Aotearoa New Zealand-based biotech companies to manufacture vaccines developed as a result of the project could result in a significant economic return and improve health outcomes for New Zealanders.

The development of an effective mucosal adjuvant could also provide a significant advantage for future COVID vaccines, she says.

The cross-disciplinary team involved in the project includes Professor Ian Hermans, deputy director of the Malaghan Institute of Medical Research, along with Professor Gavin Painter and Dr Benji Compton from the Ferrier Research Institute.

Professor La Flamme’s ground-breaking preliminary work was supported by charitable donations from the Great New Zealand Trek and individual donors to the Malaghan Institute’s multiple sclerosis research programme. Those donations also enabled the establishment of an international team for the project. As well as Professor La Flamme and Dr Zubkova, the team includes Dr Gill Webster from ImmunoStrategy and Professor Christopher Parish and Dr Anne Bruestle from the John Curtin School of Medical Research at Australian National University.