Fluzone® High-Dose Influenza Vaccine

Robertson, Corwin A.; DiazGranados, Carlos A.; Decker, Michael D.; Chit, Ayman; Mercer, Monica; Greenberg, David

doi:10.1080/14760584.2016.1254044

Cited by 49 publications

(35 citation statements)

References 58 publications

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“…Although this study met its primary objective of showing non-inferior antibody titers in older adults for IIV4 vs. IIV3, immune responses in this population were substantially lower than those observed in the younger open-label cohort that received licensed IIV3–1. Reduced immunogenicity of influenza vaccines in older adults is well documented 11 and is why a high-dose split-virion inactivated influenza vaccine (Fluzone High-Dose, Sanofi Pasteur) containing 60 µg hemagglutinin per strain 18 and a subunit vaccine containing a squalene-based oil-in-water emulsion as an adjuvant (Fluad, Sequirus) 19 have been developed specifically for this age group. These vaccines are currently trivalent, but quadrivalent formulations of both are under clinical development.…”

Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of a quadrivalent influenza vaccine in adults 65 y of age and older

Greenberg

Robertson

Talbot

et al. 2017

Human Vaccines & Immunotherapeutics

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Frequent mismatches between the predominant circulating B strain lineage and the B strain lineage in trivalent influenza vaccines have resulted in missed opportunities to prevent influenza illness. Quadrivalent influenza vaccines containing B strains from each of the 2 lineages have been developed for improved prevention of influenza B infections. Here, we describe the results of a phase III, randomized, double-blind, active-controlled, multicenter trial examining the safety and immunogenicity of a split-virion inactivated quadrivalent influenza vaccine (IIV4) in 675 adults ≥ 65 y of age (NCT01218646). Participants were randomly assigned 1:1:1 to receive a single intramuscular injection with the investigational IIV4, or one of 2 split-virion trivalent inactivated influenza vaccines (IIV3s): a licensed IIV3 containing a B Victoria-lineage strain or an investigational IIV3 containing a B Yamagata-lineage strain. Post-vaccination (day 21) hemagglutinin inhibition titers to all strains induced by IIV4 were statistically non-inferior to those induced by the 2 IIV3s. In addition, for each B strain, rates of seroconversion in the IIV4 group were superior to those induced by the comparator IIV3 not containing that B strain. For all vaccines, the most common solicited reaction was injection-site pain, and most reactions were mild to moderate in intensity and transient. Overall safety profiles were similar between IIV4 and the IIV3s, and no vaccine-related serious adverse events were reported. These results confirm that in adults ≥ 65 y of age, IIV4 was well tolerated and immunogenic against the additional B lineage strain without compromising the immunogenicity of the other 3 vaccine strains.

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Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of a quadrivalent influenza vaccine in adults 65 y of age and older

Greenberg

Robertson

Talbot

et al. 2017

Human Vaccines & Immunotherapeutics

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“…They contain 15 μg of HA per virus strain and are formulated as a trivalent vaccine (H1N1, H3N2 and influenza B) or quadrivalent vaccine (H1N1, H3N2, influenza B/victoria/2/87-lineage and influenza B/Yamagata/16/88-lineage). Some vaccine formulations, such as recombinant HA-based vaccines (Flublok) and specific formulations for elderly individuals (Fluzone high-dose), contain greater amounts of HA 182,184 . In addition, an adjuvanted vaccine formulation for elderly individuals (Fluad) is on the market 185 .…”

Section: Responses To Vaccinationmentioning

confidence: 99%

The human antibody response to influenza A virus infection and vaccination

2019

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The adaptive immune response to influenza virus infection is multifaceted and complex, involving antibody and cellular responses at both systemic and mucosal levels. Immune responses to natural infection with influenza virus in humans are relatively broad and long-lived, but influenza viruses can escape from these responses over time owing to their high mutation rates and antigenic flexibility. Vaccines are the best available countermeasure against infection, but vaccine effectiveness is low compared with other viral vaccines, and the induced immune response is narrow and short-lived. Furthermore, inactivated influenza virus vaccines focus on the induction of systemic IgG responses but do not effectively induce mucosal IgA responses. Here, I review the differences between natural infection and vaccination in terms of the antibody responses they induce and how these responses protect against future infection. A better understanding of how natural infection induces broad and long-lived immune responses will be key to developing next-generation influenza virus vaccines.

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“…In typical licensed vaccines, the dose is 15 µg of each HA protein (H1, H3, HA-B), while the vaccine specifically designed for the elderly 19 is administered at a dose of 60 µg for each HA protein.…”

Section: Introductionmentioning

confidence: 99%

Heterologous viral protein interactions within licensed seasonal influenza virus vaccines

et al. 2020

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Currently, licensed influenza virus vaccines are designed and tested only for their ability to elicit hemagglutinin (HA)-reactive, neutralizing antibodies. Despite this, the purification process in vaccine manufacturing often does not completely remove other virion components. In the studies reported here, we have examined the viral protein composition of a panel of licensed vaccines from different manufacturers and licensed in different years. Using western blotting, we found that, beyond HA proteins, there are detectable quantities of neuraminidase (NA), nucleoprotein (NP), and matrix proteins (M1) from both influenza A and influenza B viruses in the vaccines but that the composition differed by source and method of vaccine preparation. We also found that disparities in viral protein composition were associated with distinct patterns of elicited antibody specificities. Strikingly, our studies also revealed that many viral proteins contained in the vaccine form heterologous complexes. When H1 proteins were isolated by immunoprecipitation, NA (N1), M1 (M1-A), H3, and HA-B proteins were co-isolated with the H1. Further biochemical studies suggest that these interactions persist for at least 4 h at 37°C and that the membrane/intracytoplasmic domains in the intact HA proteins are important for the intermolecular interactions detected. These studies indicate that, if such interactions persist after vaccines reach the draining lymph node, both dendritic cells and HA-specific B cells may take up multiple viral proteins simultaneously. Whether these interactions are beneficial or harmful to the developing immune response will depend on the functional potential of the elicited virus-specific CD4 T cells.

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Fluzone® High-Dose Influenza Vaccine

Cited by 49 publications

References 58 publications

Safety and immunogenicity of a quadrivalent influenza vaccine in adults 65 y of age and older

Safety and immunogenicity of a quadrivalent influenza vaccine in adults 65 y of age and older

The human antibody response to influenza A virus infection and vaccination

Heterologous viral protein interactions within licensed seasonal influenza virus vaccines

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