New T-cell-based immunization procedure gives more extensive insurance against occasional flu

New T-cell-based immunization procedure gives more extensive insurance against occasional flu


  • Post By : Kumar Jeetendra

  • Source: University of Wisconsin-Madison

  • Date: 24 Sep,2020

As Americans begin pulling their sleeves up for an annual flu vaccine, researchers at the University of Wisconsin-Madison have provided new insights into an alternate vaccine approach that provides wider protection against seasonal flu.

In a study published in Cell Reports Medicine today (Sept. 22), scientists describe a T-cell-based vaccine strategy that’s effective against multiple strains of flu virus. The experimental vaccine, administered through the nose, delivered long-lasting, multi-pronged protection from the lungs of mice by rallying T-cells, specialist white blood cells which quickly eliminate viral invaders through an immune response.

The research suggests a potential strategy for creating a universal flu vaccine,”so that you do not need to make a new vaccine each year,” explains Marulasiddappa Suresh, a professor of immunology in the School of Veterinary Medicine who led the research. The researchers believe the same approach could apply to other respiratory pathogens, including the novel coronavirus that causes COVID-19.

“We do not currently have any vaccine for people on the market that could be given into the mucosa and stimulate T-cell immunity similar to this,” says Suresh, a veterinarian with specialty training in analyzing T-cell responses to viral infections.

The plan addresses the Achilles’ heel of flu vaccines, which is to attain specific antibody responses to various circulating influenza strains annually, by harnessing T-cell immunity against multiple strains. In particular, the new approach calls into activity tissue-resident memory T-cells, or TRM cells, which reside in the airways and lining of lung epithelial cells and combat invading pathogens. Like elite soldiers, TRM cells function as front line defense against infection.

Flu vaccines work by arming the immune system with an improved ability to recognize and fight off the flu virus. Vaccines introduce proteins found on the surface of influenza viruses, prompting the immune system to produce antibodies that are primed to react should the virus attack.

But because strains have to be predicted before flu season in order to produce vaccines, the vaccine in any given year may not completely match the viral strains in circulation that year. Flu viruses often mutate and can vary across time and from region to region. Additionally, protection is long-lasting nor universal.

“Although current vaccines that people get annually stimulate antibody responses, these antibodies do not cross-protect,” notes Suresh. “If there is a new flu strain not found in that year’s vaccine, the antibodies that we generated last year will not be able to protect. That’s when pandemics occur because there is a completely new strain for which we have no antibodies. That’s a really big problem in the area.”

The vaccine developed by Suresh and his group is directed against an internal protein of influenza — especially, nucleoprotein. This protein is conserved between influenza strains, meaning its genetic sequences are similar across different strains of influenza.

The vaccine also utilizes a special combination of ingredients, or adjuvants, that enhance an immune response, which the researchers developed to stimulate protective T-cells in the lungs. These adjuvants spur T-cells to form into different subtypes — in the case of the experimental influenza vaccine, memory helper T-cells and killer T-cells. By doing so, the vaccine leverages multiple modes of resistance.

Killer T-cells hunt down and kill influenza virus-infected cells. Helper T-cells assist killer T-cells and produce molecules to promote influenza control. In lab studies, the group found that both T-cell forms were needed to protect against flu.

Researchers demonstrated in a mouse model of influenza that the vaccine provides long-term immunity — at least 400 days following vaccination — from multiple influenza strains. They will next test the vaccine in ferrets and nonhuman primates, two animal models of influenza research more biologically similar to human disease and transmission.

The vaccine’s combination of adjuvants makes it adaptable to other pathogens and”expands the uterus” for vaccine research, notes Suresh. He and his team have devised ways to plan immunity to target multiple respiratory viruses.

The researchers believe the exact same vaccine technology can applied against SARS-CoV-2, the coronavirus which causes COVID-19. “Based on the COVID-19 immunology, we know this vaccine strategy would most likely work,” says Suresh.

The team is currently developing an experimental vaccine against COVID-19 and conducting laboratory tests to measure its efficacy in mice and mice, animal models for COVID-19. Initial unpublished studies in mice show that the vaccine stimulates strong T-cell immunity against COVID-19 in the lungs.\

“We didn’t previously know how to elicit these tissue-resident memory cells with a safe protein vaccine, but we now have a strategy to stimulate them in the lungs that will protect against influenza. As soon as a cell gets infected, these memory cells will kill the infected cells and the infection will be stopped in its tracks before it goes further.”Marulasiddappa Suresh, Professor of Immunology, School of Veterinary Medicine”

Together with its adaptability, this vaccine strategy may harbor important security benefits. For instance, the measles, mumps and chickenpox vaccines administered globally are live, replicating vaccines — basically benign versions of the pathogenic organism. These live vaccines stimulate strong, almost lifelong immunity. However, they can not typically be given to pregnant or immunocompromised individuals due to health risks.

In the event of the UW-Madison team’s vaccine, since it is a protein vaccine rather than a live vaccine, it should be safe for delivery to individuals that are pregnant or immunocompromised — an advantage in delivering protection to a larger patient population.

“Previously, we didn’t know how to induce T-cell immunity in the lung with no live viruses,” says Suresh. “If we cleverly use a combination adjuvant, which we have developed, you can induce T-cell immunity that should remain in the lungs and protect longer.”

Journal reference:

Marinaik, C.B., et al. (2020) Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants. Cell Reports Medicine.

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