Adjuvantation of Influenza Vaccines to Induce Cross-Protective Immunity

Abstract

Influenza poses a huge threat to global public health. Influenza vaccines are the most effective and cost-effective means to control influenza. Current influenza vaccines mainly induce neutralizing antibodies against highly variable globular head of hemagglutinin and lack cross-protection. Vaccine adjuvants have been approved to enhance seasonal influenza vaccine efficacy in the elderly and spare influenza vaccine doses. Clinical studies found that MF59 and AS03-adjuvanted influenza vaccines could induce cross-protective immunity against non-vaccine viral strains. In addition to MF59 and AS03 adjuvants, experimental adjuvants, such as Toll-like receptor agonists, saponin-based adjuvants, cholera toxin and heat-labile enterotoxin-based mucosal adjuvants, and physical adjuvants, are also able to broaden influenza vaccine-induced immune responses against non-vaccine strains. This review focuses on introducing the various types of adjuvants capable of assisting current influenza vaccines to induce cross-protective immunity in preclinical and clinical studies. Mechanisms of licensed MF59 and AS03 adjuvants to induce cross-protective immunity are also introduced. Vaccine adjuvants hold a great promise to adjuvant influenza vaccines to induce cross-protective immunity.

Precision Vaccine Development: Cues From Natural Immunity

“…This is particularly beneficial for influenza vaccines administered during a pandemic when a rapid response is required or for use in vulnerable populations, such as infants and the elderly. Up until the early 21 st century, alum remained the only adjuvant included in licensed vaccine formulations, until, in 2015 MF59 (squalene emulsion) was incorporated into a licensed influenza vaccine designed for enhancing efficacy for the elderly populations in the USA ( 215 ). MF59 triggers effective and safe immunogenicity via Th2 skewed immune responses ( 216 ) and induces chemokines and cytokines, such as CCL2, CCL3 IL-8, and IL-5 ( 217 ), which enhance vaccine efficacy by triggering memory B cells and vaccine strain specific CD4 + T cells ( 218 ).…”

“…MF59 triggers effective and safe immunogenicity via Th2 skewed immune responses ( 216 ) and induces chemokines and cytokines, such as CCL2, CCL3 IL-8, and IL-5 ( 217 ), which enhance vaccine efficacy by triggering memory B cells and vaccine strain specific CD4 + T cells ( 218 ). Adjuvant system (AS) 03 is an oil-in-water adjuvant which acts similar to MF59 ( 215 ). MF59 and AS03 adjuvants also showed heterologous immune responses against non-vaccine influenza strains in human subjects ( 215 ).…”

“…Adjuvant system (AS) 03 is an oil-in-water adjuvant which acts similar to MF59 ( 215 ). MF59 and AS03 adjuvants also showed heterologous immune responses against non-vaccine influenza strains in human subjects ( 215 ). Thus, vaccine adjuvants embrace a numerous potential to achieve a universal flu vaccine by inducing cross-protective immunity.…”

Vaccination of older adults: Influenza, pneumococcal disease, herpes zoster, COVID-19 and beyond

“…Similar effects were observed in the seasons 2004/2005 and 2005/2006 [ 54 ]. Adjuvants can improve the production of cross-reactive antibodies which recognize drifted strains (summarized in [ 55 ]), but universal influenza vaccines would be desirable to address the immense antigenic variability of influenza viruses and to be prepared for novel, potentially pandemic influenza strains. Various approaches, such as antigens based on the conserved stem-region of hemagglutinin, chimeric hemagglutinin proteins, peptides and nucleic acid platforms, are currently tested in clinical trials.…”

Physical radiofrequency adjuvant enhances immune responses to influenza H5N1 vaccination

“…13 Since its first infection of humans in 1997, H5N1 has infected more than 700 people in 15 countries in Asia, Africa, the Pacific, Europe, and Near East. 14 Mathematical modeling suggested the value of even low-efficacy targeted vaccination in the early phase of a pandemic in reducing disease transmission. 15 As such, pre-pandemic H5N1 vaccines have been stockpiled in several countries including the United States.…”