Researchers at Georgia State University have produced a novel nanoparticle-enhanced intranasal influenza vaccine. The results of a preclinical study that have just been published demonstrate the unique nasal spray induces robust local and systemic immune responses for over six months in animal models.
Inhalable nasal vaccines have long been considered a holy grail for vaccines against viruses known to take hold in a person’s upper respiratory tract. The idea is that administering vaccine antigens directly to mucous membranes in the nose could train that local tissue to more rapidly mount an immune response immediately at the point a virus enters a human body.
But producing an effective intranasal vaccine has proved a huge challenge to scientists for decades. Mucous membranes in the nose and upper respiratory tract are thick, and high doses of vaccine antigens are often needed to trigger an immune response.
In the United States there is an intranasal flu vaccine already available called FluMist and its effectiveness can vary from year to year depending on the dominant strains of influenza circulating.
FluMist is known as a live attenuated vaccine, meaning it contains real active viral particles. The virus in these kinds of vaccines has been weakened to ensure it doesn’t cause serious disease, however, there is still a chance of infection from live attenuated vaccines. So this means they are often limited to young healthy cohorts (in this case healthy subjects aged between two and 49).
This new intranasal flu vaccine takes a more traditional path, training the immune system to target a single small part of the influenza virus. In this instance the vaccine presents the immune system with a part of a protein on the surface of the influenza virus called hemagglutinin (HA).
Current flu vaccines often target the head of HA proteins but this part of the virus is known to mutate frequently, leading to the need for the vaccines to be reformulated every year. Instead of using the head of HA proteins as a vaccine antigen, newer flu vaccines in development target the stalk of these proteins. HA stalks are thought to be conserved from mutation to mutation, meaning an effective vaccine using this as its antigenic target could offer universal protection from annual influenza mutations.
The primary innovation in this new intranasal vaccine candidate from Georgia State University researchers is the creation of a complex nanoparticle that can present the immune system with HA stalk antigens alongside several other structures that amplify an immune response.
The nanoparticle is first built out of a polymer called polyethyleneimine (PEI). Then the researchers incorporated a substance known as CpG into the nanoparticle to further amplify the immune response.
“The PEI-HA/CpG nanoparticles show good potential as a cross-protective influenza vaccine candidate,” said Baozhong Wang, corresponding author on the new study. “The combination of PEI and CpG in the PEI-HA/CpG nanoparticle group contributed to the multifaceted immune responses, leading to vigorous cross protection. The incorporation of CpG and antigens into the same nanoparticle enhanced cellular immune responses.”
Early mouse studies have revealed this novel intranasal nanoparticle vaccine induced broad and robust immune responses lasting over six months. It seems the unique combination of a PEI-based nanoparticle with CpG immune-enhancement helps the HA stalk antigen trigger strong immune responses through mucosal surfaces.
First author on the study Chunhong Dong says these preliminary studies are promising but notes there still is work to be done before the vaccine is ready to move to human studies. These initial animal tests have found no adverse effects from the vaccine but more safety work is needed before clinical trials can start.
“Nanoparticle platforms have shown intriguing characteristics and great potentials in the development of next-generation cross-protective influenza vaccines,” said Dong. “However, challenges exist to the successful research and development of nanoparticle vaccines. Though no apparent adverse effects were observed in the study, a more comprehensive safety evaluation of the nanoparticle adjuvant system is needed before clinical trials.”
The new study was published in the journal ACS Applied Materials & Interfaces.
Source: Georgia State University