Immunogenicity of a monovalent, aluminum-adjuvanted influenza whole virus vaccine for pandemic use

Hehme, Norbert

doi:10.1016/s0168-1702(04)00128-5

Cited by 18 publications

(21 citation statements)

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“…Aluminum adjuvants are by far the most commonly utilized adjuvants in human vaccines and are frequently used in childhood vaccination programs in many countries (19). Recent human trials have shown their ability to enhance the immune response after influenza vaccination (3,8,9). In our study, the mice vaccinated with the low-dose aluminum-adjuvanted vaccine had significantly higher HI titers after both vaccine doses and significantly higher VN titers after the first vaccination than those vaccinated with the low-dose nonadjuvanted vaccines (i.m.…”

Section: Discussionmentioning

confidence: 99%

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Quality and Kinetics of the Antibody Response in Mice after Three Different Low-Dose Influenza Virus Vaccination Strategies

Hauge

Madhun

Haaheim

2007

Clin Vaccine Immunol

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The threat of a new influenza pandemic has led to renewed interest in dose-sparing vaccination strategies such as intradermal immunization and the use of adjuvanted vaccines. In this study we compared the quality and kinetics of the serum antibody response elicited in mice after one or two immunizations with a split influenza A (H3N2) virus, using three different low-dose vaccination strategies. The mice were divided into four groups, receiving either a low-dose vaccine (3 g hemagglutinin [HA]) intradermally or intramuscularly with or without aluminum adjuvant or the normal human vaccine dose (15 g HA) intramuscularly. Sera were collected weekly after vaccination and tested in the hemagglutination inhibition, virus neutralization, and enzyme-linked immunosorbent assays. The antibody responses induced after intradermal or intramuscular low-dose vaccinations were similar and lower than those observed after the human vaccine dose. However, low-dose adjuvanted vaccine elicited a serum antibody response comparable to that elicited by the human dose, although the second immunization did not result in any increase in cross-reactive hemagglutination inhibition antibodies, and the peak serum antibody response was observed 1 week later than in the other vaccination groups. Our murine data suggest that the low-dose intradermal route does not show any obvious advantage over the low-dose intramuscular route in inducing a serum antibody response and that none of the low-dose vaccination strategies is as effective as intramuscular vaccination with the normal human dose. However, the low-dose aluminumadjuvanted vaccine could present a feasible alternative in case of limited vaccine supply.

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Section: Discussionmentioning

confidence: 99%

“…Although other adjuvants have also proved to be effective (22), the aluminum adjuvant is the only nonproprietary alternative for influenza vaccine manufacturers. This adjuvant has shown the ability to enhance the immune response after influenza vaccination of immunologically naive subjects in several clinical trials (3,8,9,17). Recently, intradermal (i.d.)…”

mentioning

confidence: 99%

Quality and Kinetics of the Antibody Response in Mice after Three Different Low-Dose Influenza Virus Vaccination Strategies

Hauge

Madhun

Haaheim

2007

Clin Vaccine Immunol

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“…In earlier trials, Al(OH) 3 failed to confer clinically significant increases in immune responses when formulated with egg-grown subvirion (SV) inactivated vaccines. However, promising results with Al(OH) 3 have been reported with WV H5N1 vaccines [6-8]. Earlier studies suggested that some, but not all WV vaccines were more immunogenic than SV vaccines [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of inactivated, Vero cell culture-derived whole virus influenza A/H5N1 vaccine given alone or with aluminum hydroxide adjuvant in healthy adults

Keitel

Dekker

Mink

et al. 2009

Vaccine

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Dosage-sparing strategies, adjuvants and alternative substrates for vaccine production are being explored for influenza vaccine development. We assessed the safety and immunogenicity of a Vero cell culture-grown inactivated whole virus influenza A/H5N1 vaccine with or without aluminum hydroxide adjuvant [Al(OH) 3 ] in healthy young adults. Vaccines were well tolerated, but injection site discomfort was more frequent in groups receiving Al(OH) 3 . Dose-related increases in serum antibody levels were observed. Neutralizing antibody titers varied significantly when tested by two different laboratories. Al(OH) 3 did not enhance HAI or neutralizing antibody responses, and contributed to increased injection site pain. Because influenza antibody titers vary significantly between different laboratories, international standardization of assays is warranted.

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“…Another approach is to add adjuvants (3) in order to induce or augment antibody responses that can provide cross-protection against antigenically drifted strains or even full heterosubtypic immunity, in which vaccination with antigens from one viral subtype (e.g., H3N2) protects from a different subtype (e.g., H1N1 or H5N1) (27). Such strategies might also allow dose sparing, i.e., whereby the amount of antigen and the number of administered doses could be reduced to achieve a protective immune responses (29).…”

mentioning

confidence: 99%

Cationic Lipid/DNA Complex-Adjuvanted Influenza A Virus Vaccination Induces Robust Cross-Protective Immunity

Hong

Chang

Botham

et al. 2010

J Virol

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Influenza A virus is a negative-strand segmented RNA virus in which antigenically distinct viral subtypes are defined by the hemagglutinin (HA) and neuraminidase (NA) major viral surface proteins. An ideal inactivated vaccine for influenza A virus would induce not only highly robust strain-specific humoral and T-cell immune responses but also cross-protective immunity in which an immune response to antigens from a particular viral subtype (e.g., H3N2) would protect against other viral subtypes (e.g., H1N1). Cross-protective immunity would help limit outbreaks from newly emerging antigenically novel strains. Here, we show in mice that the addition of cationic lipid/noncoding DNA complexes (CLDC) as adjuvant to whole inactivated influenza A virus vaccine induces significantly more robust adaptive immune responses both in quantity and quality than aluminum hydroxide (alum), which is currently the most widely used adjuvant in clinical human vaccination. CLDCadjuvanted vaccine induced higher total influenza virus-specific IgG, particularly for the IgG2a/c subclass. Higher levels of multicytokine-producing influenza virus-specific CD4 and CD8 T cells were induced by CLDC-adjuvanted vaccine than with alum-adjuvanted vaccine. Importantly, CLDC-adjuvanted vaccine provided significant cross-protection from either a sublethal or lethal influenza A viral challenge with a different subtype than that used for vaccination. This superior cross-protection afforded by the CLDC adjuvant required CD8 T-cell recognition of viral peptides presented by classical major histocompatibility complex class I proteins. Together, these results suggest that CLDC has particular promise for vaccine strategies in which T cells play an important role and may offer new opportunities for more effective control of human influenza epidemics and pandemics by inactivated influenza virus vaccine.

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Immunogenicity of a monovalent, aluminum-adjuvanted influenza whole virus vaccine for pandemic use

Cited by 18 publications

References 0 publications

Quality and Kinetics of the Antibody Response in Mice after Three Different Low-Dose Influenza Virus Vaccination Strategies

Quality and Kinetics of the Antibody Response in Mice after Three Different Low-Dose Influenza Virus Vaccination Strategies

Safety and immunogenicity of inactivated, Vero cell culture-derived whole virus influenza A/H5N1 vaccine given alone or with aluminum hydroxide adjuvant in healthy adults

Cationic Lipid/DNA Complex-Adjuvanted Influenza A Virus Vaccination Induces Robust Cross-Protective Immunity

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