Immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1, NIBRG-14) vaccine administered by intramuscular or subcutaneous injection

Ikeno, Daisuke; Kimachi, Kazuhiko; Kino, Yoichiro; Harada, Seiichi; Yoshida, Kayo; Tochihara, Shinji; Itamura, Shigeyuki; Odagiri, Takato; Tashiro, Masato; Okada, Kenji; Miyazaki, Chiaki; Ueda, Kohji

doi:10.1111/j.1348-0421.2009.00191.x

Cited by 18 publications

(18 citation statements)

References 22 publications

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“…For example, in human subjects, ID delivery of a DNA vaccine at a lower dose (10% of a full dose) or SC delivery of a full dose was similarly associated with mild local pruritus (itchiness), superficial skin lesions, and injection site nodules but no local site reactions were observed following IM injection[92]. For an alum-adjuvanted inactivated whole-virion influenza A vaccine in adult men[93] and a diphtheria and tetanus toxoids (DT) vaccine in children[94], local adverse events were less severe with IM injection compared with SC injection. Another study showed similar levels of local reactions upon IM or SC administration of two doses of MMRV combination vaccine in healthy children[95].…”

Section: Introductionmentioning

confidence: 99%

Effect of vaccine administration modality on immunogenicity and efficacy

Zhang

Wang

2015

Expert Review of Vaccines

197

149

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Summary The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: (1) features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant, and dosing; (2) individual variations among vaccine recipients; and (3) vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route, and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines.

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Section: Introductionmentioning

confidence: 99%

Effect of vaccine administration modality on immunogenicity and efficacy

Zhang

Wang

2015

Expert Review of Vaccines

197

149

View full text Add to dashboard Cite

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“…Some of the avian virus vaccines were tested with and without an adjuvant. Alum as an adjuvant varied in induction of increases in responses; however, use of the adjuvants AS03 and MF59 uniformly resulted in major increases in response frequencies [3], [5], [7]–[9], [11], [13]–[23], [26], [27], [29].To try and understand the basis for the apparent immunizing deficiency of avian influenza virus vaccines without adjuvant, we sought alternative laboratory correlates for immune responses in humans. The findings of these efforts constitute the basis for this report.…”

Section: Introductionmentioning

confidence: 99%

Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans

et al. 2012

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BackgroundSerum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses.DesignTo help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM).ResultsAntigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were <1∶4 for the H7 vaccine and 1∶661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1) vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2) vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1) vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7) vaccine contained mostly small 5 to 20 nm structures.SummaryAntigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.

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“…However, many of these antigens induce relatively low levels of functional neutralizing antibody when tested clinically121314, which prompted testing of additional pandemic vaccine formulations containing adjuvants15. The most commonly used adjuvants in clinical stage H5N1 vaccines are alum (Alhydrogel, Adju-Phos ® ) and oil-in-water emulsions containing squalene1617181920212223242526272829303132. Emulsion-adjuvanted H5N1 vaccines have been thoroughly tested clinically, and have been shown to improve vaccine potency, and to provide critical dose sparing functions.…”

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confidence: 99%

A Formulated TLR7/8 Agonist is a Flexible, Highly Potent and Effective Adjuvant for Pandemic Influenza Vaccines

Hoeven

Fox

Granger

et al. 2017

Sci Rep

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Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models. However, many of these agonist molecules have proven difficult to develop clinically. Here, we describe comprehensive adjuvant formulation development of the imidazoquinoline TLR-7/8 agonist 3M-052, in combination with H5N1 hemagglutinin (HA) based antigens. We find that 3M-052 in multiple formulations protects both mice and ferrets from lethal H5N1 homologous virus challenge. Furthermore, we conclusively demonstrate the ability of 3M-052 adjuvant formulations to broaden responses to H5N1 HA based antigens, and show that this broadening is functional using a heterologous lethal virus challenge in ferrets. Given the extensive clinical use of imidazoquinoline TLR agonists for other indications, these studies identify multiple adjuvant formulations which may be rapidly advanced into clinical trials in an H5N1 vaccine.

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Immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1, NIBRG-14) vaccine administered by intramuscular or subcutaneous injection

Cited by 18 publications

References 22 publications

Effect of vaccine administration modality on immunogenicity and efficacy

Effect of vaccine administration modality on immunogenicity and efficacy

Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans

A Formulated TLR7/8 Agonist is a Flexible, Highly Potent and Effective Adjuvant for Pandemic Influenza Vaccines

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