Intranasal Nanoparticle Flu Vaccine Boosts Immune Response in Mice

By Marilynn Larkin

May 13, 2021

NEW YORK (Reuters Health) - An intranasal influenza vaccine made of nanoparticles enhanced the immune response and offered protection against different viral strains in mice, and also shows promise for people, researchers say.

"The polyethyleneimine (PEI)-functionalized graphene oxide nanoparticle (GP nanoparticles) vaccine significantly/potently boosted the induced immune responses to influenza hemagglutinin (HA) antigens in an intranasal route, conferring cross-protection against homologous and heterologous influenza viral infections," Dr. Chunhong Dong of Georgia State University in Atlanta told Reuters Health by email. However, she said, the mechanisms by which the enhancement occurred are still unknown, and need to be studied further before robust universal influenza vaccines can be developed.

For the current study, published in Proceedings of the National Academy of Sciences of the United States of America, the researchers developed an intranasal influenza vaccine using recombinant HA as the antigen component. They also created the two-dimensional nanomaterial - the PEI-functionalized GP nanoparticles referred to by Dr. Dong - and found that it displayed potent adjuvant effects on intranasally-delivered influenza vaccines in mice.

Specifically, after intranasal immunization, GP nanoparticle formulations induced significantly enhanced and cross-reactive immune responses at both systemic sites and mucosal surfaces in mice. And, even without any additional adjuvant, they boosted both antigen-specific humoral and cellular immune responses, comparable to those induced by CpG, an acknowledged potent mucosal immunomodulator.

Further, the authors note, the GP nanoplatform "can be easily adapted for constructing mucosal vaccines for different respiratory pathogens."

Nonetheless, Dr. Dong said, "The safety profiles of ...nanoparticles need further systematic preclinical evaluation. Despite no apparent adverse effects observed in our simple safety study, a more comprehensive assessment is needed before future clinical trials."

"In addition," she said, "despite the superior logistical advantages of the needle-free intranasal influenza vaccines over traditional injectable vaccines, some patients who have allergic rhinitis or sensitivity to the GO nanomaterials may not be good candidates for the intranasal approach."

Dr. Henry Cohen, Dean and Professor at Touro College of Pharmacy in New York City, commented on the study in an email to Reuters Health. "The nanoparticles approach for intranasal administration elicits a systemic and local immune response, which provides improved protection at the primary port of infectious entry (the nose). Injectable vaccines generally fail to achieve a potent local (nasal) immune response; hence, efficacy might improve with an intranasal vaccine."

"A caveat," he said, "is that intranasal (vaccination) requires appropriate administration technique, and good hand dexterity and hand, nose and eye coordination, which may be difficult for some elderly patients and those with arthritis. In addition, to ensure vaccine compliance and documentation in medical records, direct observation by the pharmacist or physician will still be required."

In the U.S. and Europe, intranasal vaccines have been known to cause irritation and allergic effects, he noted, including runny nose, headache and cough. "These side effects are usually mild and short-lived. The nasal vaccine excipients, buffers, and adjuvants may also elicit a systemic response causing respiratory and pulmonary problems or even central nervous system effects."

"Of note," he added, "there is only one intranasal flu vaccine currently recommended by the Advisory Committee on Immunization Practices in the U.S., FluMist Quadrivalent. This vaccine was recommended in 2018-2019 and 2020-2021, (but) not in 2016-2017 and 2017-2018 due to lack of efficacy."

Dr. Sharon Nachman, Chief of the Division of Pediatric Infectious Diseases at Stony Brook Children's Hospital in New York, noted in an email to Reuters Health that a nasal formulation of a COVID-19 vaccine "might be very helpful on the path towards herd immunity, and might be more efficient at getting everyone vaccinated (either directly or indirectly)."

SOURCE: https://bit.ly/3w2ShVq Proceedings of the National Academy of Sciences of the United States of America, online May 11, 2021.

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