tetano
Editor, Senior Moderator
Vaccine. 2019 May 9. pii: S0264-410X(19)30562-6. doi: 10.1016/j.vaccine.2019.04.074. [Epub ahead of print]
[h=1]mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.[/h] Feldman RA[SUP]1[/SUP], Fuhr R[SUP]2[/SUP], Smolenov I[SUP]3[/SUP], Mick Ribeiro A[SUP]3[/SUP], Panther L[SUP]4[/SUP], Watson M[SUP]5[/SUP], Senn JJ[SUP]6[/SUP], Smith M[SUP]7[/SUP], Almarsson Ӧ[SUP]8[/SUP], Pujar HS[SUP]9[/SUP], Laska ME[SUP]3[/SUP], Thompson J[SUP]10[/SUP], Zaks T[SUP]11[/SUP], Ciaramella G[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses.
[h=4]METHODS:[/h] Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18-64 years for H10N8 study; 18-49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 ?g and intradermal dose levels of 25 and 50 ?g were evaluated. H7N9 IM 10-, 25-, and 50-?g dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay).
[h=4]RESULTS:[/h] H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-?g IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-?g intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 ?g achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-?g groups and 96.6% in the 50-?g group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 ?g IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 ?g). Significant cell-mediated responses were not detected in either study.
[h=4]CONCLUSIONS:[/h] The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses. ClinicalTrials.gov NCT03076385 and NCT03345043.
Copyright ? 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.
[h=4]KEYWORDS:[/h] Immunogenicity; Pandemic influenza; Safety; Vaccines; mRNA
PMID: 31079849 DOI: 10.1016/j.vaccine.2019.04.074
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[h=1]mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.[/h] Feldman RA[SUP]1[/SUP], Fuhr R[SUP]2[/SUP], Smolenov I[SUP]3[/SUP], Mick Ribeiro A[SUP]3[/SUP], Panther L[SUP]4[/SUP], Watson M[SUP]5[/SUP], Senn JJ[SUP]6[/SUP], Smith M[SUP]7[/SUP], Almarsson Ӧ[SUP]8[/SUP], Pujar HS[SUP]9[/SUP], Laska ME[SUP]3[/SUP], Thompson J[SUP]10[/SUP], Zaks T[SUP]11[/SUP], Ciaramella G[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses.
[h=4]METHODS:[/h] Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18-64 years for H10N8 study; 18-49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 ?g and intradermal dose levels of 25 and 50 ?g were evaluated. H7N9 IM 10-, 25-, and 50-?g dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay).
[h=4]RESULTS:[/h] H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-?g IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-?g intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 ?g achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-?g groups and 96.6% in the 50-?g group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 ?g IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 ?g). Significant cell-mediated responses were not detected in either study.
[h=4]CONCLUSIONS:[/h] The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses. ClinicalTrials.gov NCT03076385 and NCT03345043.
Copyright ? 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.
[h=4]KEYWORDS:[/h] Immunogenicity; Pandemic influenza; Safety; Vaccines; mRNA
PMID: 31079849 DOI: 10.1016/j.vaccine.2019.04.074
Free full text