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Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration.
Vaccine. 2009 Jun 02; 27(27):3561-7.V

Abstract

BACKGROUND

Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced antigen doses similar to that observed after i.m. full dose vaccination.

METHODS

In a randomized, partially blinded phase II study 224, healthy adults aged >or=18 to <or=60 years were randomly assigned to four groups and received trivalent influenza vaccine at single doses of 3.0, 4.5 and 6.0 microg hemagglutinin (HA) antigen of each influenza virus strain via i.d. injection or 15.0 microg HA of each influenza strain via i.m. delivery. Serum anti-influenza virus antibodies were determined by hemagglutination inhibition (HI) assay before and 3 weeks after vaccination. Safety assessments were made at baseline and at the follow-up visit by the investigators and for a 4-day period post-vaccination by the subjects themselves.

RESULTS

The EMEA requirements for re-licensing of influenza vaccines were fulfilled in all groups 3 weeks after vaccination, irrespective of dose and mode of administration. High seroconversion rates were observed in all study groups and for all strains ranging from 50.9 to 85.5% and 70.4 to 87.0% after i.d. and i.m. vaccination, respectively. Seroprotection rates for the A strains A/Solomon Islands and A/Wisconsin were generally higher compared to the B/Malaysia strain and ranged from 89.1 to 98.2% across the i.d. groups. Similar rates of 96.3% for the A/Solomon Islands and 94.4% for the A/Wisconsin strain were observed in the i.m. group. Seroprotection rates for the B/Malaysia strain were 65.5, 83.0 and 72.7% after i.d. administration of 3.0, 4.5, and 6.0 microg HA of each strain, respectively, compared to a seroprotection rate of 85.2% in the i.m. group. In addition, marked increases in geometric mean titer (GMT) were observed across the groups for all influenza virus strains ranging from 6.9 to 70.5 for i.d. and from 16.9 to 56.5 for i.m. antigen delivery. Both routes of administration were well tolerated. Systemic reactions were broadly similar across the groups. With respect to local reactions the frequency of injection site pain and ecchymosis were significantly lower following i.d. vaccination, while other local reactions such as erythema occurred at higher rates with i.d. than with i.m. vaccine administration, as expected due to the mechanism of action for the i.d. route.

CONCLUSIONS

The virosomal adjuvanted influenza vaccine (Inflexal V) was shown to be overall highly immunogenic and well tolerated when given i.d. at reduced doses to healthy adults, eliciting an immune response similar to that observed with full dose i.m. administration and thus suggesting a promising antigen-sparing strategy for universal influenza vaccination against endemic influenza.

TRIAL REGISTRATION

ISRCTN registry number: 33950739.

Authors+Show Affiliations

Crucell, Berna Biotech Ltd, 3018 Berne, Switzerland. valerie.kuenzi@crucell.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

19464535

Citation

Künzi, Valérie, et al. "Immunogenicity and Safety of Low Dose Virosomal Adjuvanted Influenza Vaccine Administered Intradermally Compared to Intramuscular Full Dose Administration." Vaccine, vol. 27, no. 27, 2009, pp. 3561-7.
Künzi V, Klap JM, Seiberling MK, et al. Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration. Vaccine. 2009;27(27):3561-7.
Künzi, V., Klap, J. M., Seiberling, M. K., Herzog, C., Hartmann, K., Kürsteiner, O., Kompier, R., Grimaldi, R., & Goudsmit, J. (2009). Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration. Vaccine, 27(27), 3561-7. https://doi.org/10.1016/j.vaccine.2009.03.062
Künzi V, et al. Immunogenicity and Safety of Low Dose Virosomal Adjuvanted Influenza Vaccine Administered Intradermally Compared to Intramuscular Full Dose Administration. Vaccine. 2009 Jun 2;27(27):3561-7. PubMed PMID: 19464535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration. AU - Künzi,Valérie, AU - Klap,Jaco M, AU - Seiberling,Michael K, AU - Herzog,Christian, AU - Hartmann,Katharina, AU - Kürsteiner,Oliver, AU - Kompier,Ronald, AU - Grimaldi,Roberto, AU - Goudsmit,Jaap, Y1 - 2009/04/10/ PY - 2009/01/12/received PY - 2009/03/17/revised PY - 2009/03/23/accepted PY - 2009/5/26/entrez PY - 2009/5/26/pubmed PY - 2009/7/22/medline SP - 3561 EP - 7 JF - Vaccine JO - Vaccine VL - 27 IS - 27 N2 - BACKGROUND: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced antigen doses similar to that observed after i.m. full dose vaccination. METHODS: In a randomized, partially blinded phase II study 224, healthy adults aged >or=18 to <or=60 years were randomly assigned to four groups and received trivalent influenza vaccine at single doses of 3.0, 4.5 and 6.0 microg hemagglutinin (HA) antigen of each influenza virus strain via i.d. injection or 15.0 microg HA of each influenza strain via i.m. delivery. Serum anti-influenza virus antibodies were determined by hemagglutination inhibition (HI) assay before and 3 weeks after vaccination. Safety assessments were made at baseline and at the follow-up visit by the investigators and for a 4-day period post-vaccination by the subjects themselves. RESULTS: The EMEA requirements for re-licensing of influenza vaccines were fulfilled in all groups 3 weeks after vaccination, irrespective of dose and mode of administration. High seroconversion rates were observed in all study groups and for all strains ranging from 50.9 to 85.5% and 70.4 to 87.0% after i.d. and i.m. vaccination, respectively. Seroprotection rates for the A strains A/Solomon Islands and A/Wisconsin were generally higher compared to the B/Malaysia strain and ranged from 89.1 to 98.2% across the i.d. groups. Similar rates of 96.3% for the A/Solomon Islands and 94.4% for the A/Wisconsin strain were observed in the i.m. group. Seroprotection rates for the B/Malaysia strain were 65.5, 83.0 and 72.7% after i.d. administration of 3.0, 4.5, and 6.0 microg HA of each strain, respectively, compared to a seroprotection rate of 85.2% in the i.m. group. In addition, marked increases in geometric mean titer (GMT) were observed across the groups for all influenza virus strains ranging from 6.9 to 70.5 for i.d. and from 16.9 to 56.5 for i.m. antigen delivery. Both routes of administration were well tolerated. Systemic reactions were broadly similar across the groups. With respect to local reactions the frequency of injection site pain and ecchymosis were significantly lower following i.d. vaccination, while other local reactions such as erythema occurred at higher rates with i.d. than with i.m. vaccine administration, as expected due to the mechanism of action for the i.d. route. CONCLUSIONS: The virosomal adjuvanted influenza vaccine (Inflexal V) was shown to be overall highly immunogenic and well tolerated when given i.d. at reduced doses to healthy adults, eliciting an immune response similar to that observed with full dose i.m. administration and thus suggesting a promising antigen-sparing strategy for universal influenza vaccination against endemic influenza. TRIAL REGISTRATION: ISRCTN registry number: 33950739. SN - 0264-410X UR - https://www.unboundmedicine.com/medline/citation/19464535/Immunogenicity_and_safety_of_low_dose_virosomal_adjuvanted_influenza_vaccine_administered_intradermally_compared_to_intramuscular_full_dose_administration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(09)00487-3 DB - PRIME DP - Unbound Medicine ER -