Infect Chemother.  2013 Jun;45(2):159-174. 10.3947/ic.2013.45.2.159.

Fluad(R)-MF59(R)-Adjuvanted Influenza Vaccine in Older Adults

• Tsai TF

• KMID: 2284997
• DOI: http://doi.org/10.3947/ic.2013.45.2.159

Abstract

Influenza directly or indirectly contributes to the four leading causes of global mortality, at rates that are highest in older adults. As the proportion of older adults in the Korean population is greater than in most other countries, influenza prevention is a greater public health priority in Korea than elsewhere. Conventional inactivated influenza vaccine (IIV) is less immunogenic and efficacious (-50%) in older than in young adults, but adjuvanting the vaccine with oil-in-water emulsion MF59(R) increases immunogenicity, resulting in comparatively higher levels of hemagglutination inhibition antibodies and greater protection against all influenza, as well as cases requiring hospitalization. A recent observational study demonstrated that the adjuvanted vaccine protected older adults against influenza in a year when nonadjuvanted IIV was ineffective. In another multiyear study, the adjuvanted vaccine was estimated to be 25% more effective in preventing pneumonia and influenza hospitalizations compared to nonadjuvanted vaccine. Although MF59-adjuvanted vaccine is transiently more reactogenic than nonadjuvanted vaccine, there is no evidence that it increases risks for serious adverse events, including those with an autoimmune etiology. Experience thus far indicates a favorable balance of benefit to risk for MF59. This may reflect the adjuvant's mechanism of action in which the squalene oil emulsion increases antibody responses to co-administered antigen without acting more generally as an immunopotentiator.

Keyword

Influenza; Influenza vaccine; MF59; Emulsion adjuvant; Adjuvant

MeSH Terms

Adult
Antibodies
Antibody Formation
Hemagglutination
Hospitalization
Humans
Influenza Vaccines
Influenza, Human
Korea
Pneumonia
Polysorbates
Public Health
Squalene
Young Adult
Antibodies
Influenza Vaccines
Polysorbates
Squalene

Figure

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  Figure 1 Proportion of population 65 years and older, by country, reported and projected by year.

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  Figure 2 Comparative hemagglutination inhibition antibody responses to MF59-adjuvanted and nonadjuvanted inactivated influenza vaccine in older adults, by subtype. Immune responses vary according to strain and season.

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  Figure 3 Seroprotection (SP) and seroconversion (SC) in adults ≥ 75 year old, by serotype. Inactivated influenza vaccine (IIV3), adjuvanted IIV (IIVa3).

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  Figure 4 Postvaccination GMT ratio following subsequent yearly vaccination of a cohort of elderly subjects (≥ 65 years of age) (2).

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  Figure 5 Hemagglutination inhibition (HI) antibody responses to vaccine (A/Wyoming/3/03(H3N2) and H3N2 strains appearing in subsequent years in elderly adjuvanted and non-adjuvanted vaccine recipients-proportion with HI titers > 40. Committee for Medicinal Products for Human Use (CHMP) IIV3, trivalent inactivated influenza vaccine; IIVa3, MF59 adjuvanted trivalent inactivated influenza vaccine.

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  Figure 6 Age-specific hospitalizations for influenza-related illness, US, by week, 2012-13 season (http://www.cdc.gov/flu/weekly/).

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  Figure 7 Influenza-related hospitalizatons, US, 2012-13 season by age group and underlying medical condition (http://www.cdc.gov/flu/weekly/).

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  Figure 8 Lombardy influenza effectiveness (LIVE) study. Although influenza hospitalizations were not laboratory confirmed, reductions in hospitalizations among adjuvanted vaccine recipients increased and became significant as the analysis focused on peak weeks of influenza transmission, suggesting a specific effect on hospitalizations due to influenza. IIV3, trivalent inactivated influenza vaccine; IIVa3, MF59 adjuvanted trivalent inactivated influenza vaccine.

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  Figure 9 Solicited adverse events in older adults receiving MF59-adjuvanted or nonadjuvanted seasonal influenza vaccine over three consecutive years. IIV3, trivalent inactivated influenza vaccine; IIVa3, MF59 adjuvanted trivalent inactivated influenza vaccine.

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  Figure 10 Solicited, unsolicited and serious adverse events in subjects receiving MF59-adjuvanted or non-adjuvanted seasonal influenza vaccine by adverse event category with risk ratios.

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  Figure 11 MF59 emulsion adjuvant and its constituents.

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  Figure 12 Summary of the mechanism of action of MF59 adjuvant.

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