Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: A Phase 1 dose-escalation study in healthy adults

Cummings, James F.; Guerrero, Melanie; Moon, James E.; Waterman, Paige; Nielsen, Robin; Jefferson, Stacie; Gross, F. Liaini; Hancock, Kathy; Katz, Jacqueline M.; Yusibov, Vidadi

doi:10.1016/j.vaccine.2013.10.017

Cited by 90 publications

(60 citation statements)

References 41 publications

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“…A post-hoc analysis of MN antibody responses using a cut-off titer of ≥10 revealed responses that were high among responders, which is suggestive of a threshold-like effect that may be further enhanced. Furthermore, the results of a completed Phase 1 trial of plant-produced HAC1 influenza vaccine (recombinant HA derived from A/California/04/2009 [H1N1] strain of influenza A virus) have demonstrated that HAC1 is immunogenic when compared with a licensed, egg-derived H1N1 vaccine [52]. Therefore, and as further supported by studies of conventional egg-derived H5N1 vaccines and recombinant H5N1 vaccines produced in other expression systems, the underwhelming results observed with the HAI-05 vaccine in this study appear to be related to the H5 antigen itself.…”

Section: Resultsmentioning

confidence: 99%

Safety and Immunogenicity of a Plant-Produced Recombinant Hemagglutinin-Based Influenza Vaccine (HAI-05) Derived from A/Indonesia/05/2005 (H5N1) Influenza Virus: A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study in Healthy Adults

Chichester

Jones

Green

et al. 2012

Viruses

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Recently, we have reported [1,2] on a subunit influenza vaccine candidate based on the recombinant hemagglutinin protein from the A/Indonesia/05/2005 (H5N1) strain of influenza virus, produced it using ‘launch vector’-based transient expression technology in Nicotiana benthamiana, and demonstrated its immunogenicity in pre-clinical studies. Here, we present the results of a first-in-human, Phase 1 randomized, double-blind, placebo-controlled study designed to investigate safety, reactogenicity and immunogenicity of three escalating dose levels of this vaccine, HAI-05, (15, 45 and 90 µg) adjuvanted with Alhydrogel® (0.75 mg aluminum per dose) and the 90 µg dose level without Alhydrogel®. Vaccine was administered intramuscularly in two injections three weeks apart to healthy adults of 18–49 years of age. At all dose levels the vaccine was generally safe and well tolerated, with no reported serious adverse events or dose-limiting toxicities. Mild local and systemic reactions were observed in all vaccine dose groups and the placebo group and their occurrence was not dose related. The incidence rates were higher in the groups receiving vaccine with Alhydrogel®. The immune response elicited by the HAI-05 vaccine was variable with respect to both hemagglutination-inhibition and virus microneutralization antibody titers, with the highest responses observed in the 90 µg unadjuvanted group.

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Section: Resultsmentioning

confidence: 99%

Safety and Immunogenicity of a Plant-Produced Recombinant Hemagglutinin-Based Influenza Vaccine (HAI-05) Derived from A/Indonesia/05/2005 (H5N1) Influenza Virus: A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study in Healthy Adults

Chichester

Jones

Green

et al. 2012

Viruses

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“…Subunit vaccines based on the full-length HA protein have shown their ability to induce protective immunity in preclinical tests and clinical trials [82]. For example, immunization with a baculovirus system-expressed recombinant protein (rH5HA) against the HA of a highly pathogenic classic H5N1 influenza virus protected mice from lethal challenge against pathogenic avian influenza virus, and the serum antibody lasted more than 6 months [83].…”

Section: Advancements In the Development Of Subunit Influenza Vaccmentioning

confidence: 99%

“…For example, immunization with a baculovirus system-expressed recombinant protein (rH5HA) against the HA of a highly pathogenic classic H5N1 influenza virus protected mice from lethal challenge against pathogenic avian influenza virus, and the serum antibody lasted more than 6 months [83]. Other studies have reported that a plant-produced subunit influenza vaccine, HAC1, based on the recombinant HA of 2009 pandemic A/California/04/2009 (H1N1) strain, demonstrated immunogenicity and safety in Phase I clinical trials of healthy adults [82]. …”

Section: Advancements In the Development Of Subunit Influenza Vaccmentioning

confidence: 99%

“…In addition to the above vaccine types, an increased number of protein-based subunit vaccines under clinical trials has shown good safety, tolerance and efficacy. For example, a plant-expressed recombinant protein, HAC1, which contains HA of A/California/04/2009(H1N1) strain, was shown to be effective in inducing neutralizing antibody responses in immunized healthy adults against virus infection [82]. In another case, HAI-05, a recombinant HA protein from A/Indonesia/05/2005(H5N1) was proven to be safe in healthy adults of 18-49 years old and induce specific anti-H5N1 immune responses [114].…”

Section: Clinically Trialed and Licensed Influenza Vaccinesmentioning

confidence: 99%

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Advancements in the development of subunit influenza vaccines

Zhang

Zheng

et al. 2015

Microbes and Infection

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The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines.

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“…12,32 During the synthesis, sequence encoding the signal peptide of HA (a.a. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] was replaced by the sequence encoding the signal peptide of CA from N. tabacum. To obtain the construct pGRD4-CA-HACTMhT, the TM and CT domains were replaced by heterologous sequences.…”

Section: Construction and Production Of Influenza Hac-vlps In Plantsmentioning

confidence: 99%

Immunogenicity of H1N1 influenza virus-like particles produced inNicotiana benthamiana

Shoji

Prokhnevsky²,

Leffet³

et al. 2014

Human Vaccines & Immunotherapeutics

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Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: A Phase 1 dose-escalation study in healthy adults

Cited by 90 publications

References 41 publications

Safety and Immunogenicity of a Plant-Produced Recombinant Hemagglutinin-Based Influenza Vaccine (HAI-05) Derived from A/Indonesia/05/2005 (H5N1) Influenza Virus: A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study in Healthy Adults

Safety and Immunogenicity of a Plant-Produced Recombinant Hemagglutinin-Based Influenza Vaccine (HAI-05) Derived from A/Indonesia/05/2005 (H5N1) Influenza Virus: A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study in Healthy Adults

Advancements in the development of subunit influenza vaccines

Immunogenicity of H1N1 influenza virus-like particles produced inNicotiana benthamiana

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