tetano
Editor, Senior Moderator
Open Forum Infect Dis. 2014 Nov 18;1(3)
fu102. doi: 10.1093/ofid/ofu102. eCollection 2014.
[h=1]Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial.[/h] Mulligan MJ, Bernstein DI, Frey S, Winokur P, Rouphael N, Dickey M, Edupuganti S, Spearman P, Anderson E, Graham I, Noah DL, Mangal B, Kim S, Hill H, Whitaker J[SUP]1[/SUP], Emery W[SUP]1[/SUP], Beck A[SUP]1[/SUP], Stephens K[SUP]1[/SUP], Hartwell B[SUP]1[/SUP], Ogilvie M[SUP]1[/SUP], Rimann N[SUP]1[/SUP], Osinski E[SUP]1[/SUP], Destefano E[SUP]1[/SUP], Gajadhar T[SUP]1[/SUP], Strudwick A[SUP]1[/SUP], Pierce K[SUP]1[/SUP], Lai L[SUP]1[/SUP], Yue L[SUP]1[/SUP], Wang D[SUP]1[/SUP], Ying C[SUP]1[/SUP], Cline A[SUP]1[/SUP], Foltz T[SUP]1[/SUP], Wagner N[SUP]1[/SUP], Dull G[SUP]1[/SUP], Pacatte T[SUP]1[/SUP], Taggart B[SUP]1[/SUP], Johnson V[SUP]1[/SUP], Haller L[SUP]1[/SUP], Looney C[SUP]1[/SUP], Li S[SUP]1[/SUP], May M[SUP]1[/SUP], Myers B[SUP]1[/SUP], May R[SUP]1[/SUP], Parker L[SUP]1[/SUP], Cochran N[SUP]1[/SUP], Bowen D[SUP]1[/SUP], Bell M[SUP]1[/SUP], Scoggins J[SUP]1[/SUP], Burns A[SUP]1[/SUP], Stablein C[SUP]1[/SUP], Wolff M[SUP]1[/SUP], Jolles B[SUP]1[/SUP], Leung B[SUP]1[/SUP], Lambert L[SUP]1[/SUP], Shorer S[SUP]1[/SUP], Buchanan W[SUP]1[/SUP], Murray S[SUP]1[/SUP], Chang S[SUP]1[/SUP], Gorman R[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs.
[h=4]METHODS:[/h] A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant. Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18-49 years.
[h=4]RESULTS:[/h] Two hundred and seventy subjects were enrolled. After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001). Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher. Vaccine + MF59 produced cross-reactive antibody responses against 4 heterologous H5N1 viruses. Excellent safety and tolerability were demonstrated.
[h=4]CONCLUSIONS:[/h] Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe. The feasibility of the point-of-use mixing should be studied further.
[h=4]KEYWORDS:[/h] H5N1; MF59; adjuvant; antibody; avian influenza; pandemic preparedness; point-of-use mixing; vaccine
PMID: 25734170 [PubMed] PMCID: PMC4324215 Free PMC Article
fu102. doi: 10.1093/ofid/ofu102. eCollection 2014.[h=1]Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial.[/h] Mulligan MJ, Bernstein DI, Frey S, Winokur P, Rouphael N, Dickey M, Edupuganti S, Spearman P, Anderson E, Graham I, Noah DL, Mangal B, Kim S, Hill H, Whitaker J[SUP]1[/SUP], Emery W[SUP]1[/SUP], Beck A[SUP]1[/SUP], Stephens K[SUP]1[/SUP], Hartwell B[SUP]1[/SUP], Ogilvie M[SUP]1[/SUP], Rimann N[SUP]1[/SUP], Osinski E[SUP]1[/SUP], Destefano E[SUP]1[/SUP], Gajadhar T[SUP]1[/SUP], Strudwick A[SUP]1[/SUP], Pierce K[SUP]1[/SUP], Lai L[SUP]1[/SUP], Yue L[SUP]1[/SUP], Wang D[SUP]1[/SUP], Ying C[SUP]1[/SUP], Cline A[SUP]1[/SUP], Foltz T[SUP]1[/SUP], Wagner N[SUP]1[/SUP], Dull G[SUP]1[/SUP], Pacatte T[SUP]1[/SUP], Taggart B[SUP]1[/SUP], Johnson V[SUP]1[/SUP], Haller L[SUP]1[/SUP], Looney C[SUP]1[/SUP], Li S[SUP]1[/SUP], May M[SUP]1[/SUP], Myers B[SUP]1[/SUP], May R[SUP]1[/SUP], Parker L[SUP]1[/SUP], Cochran N[SUP]1[/SUP], Bowen D[SUP]1[/SUP], Bell M[SUP]1[/SUP], Scoggins J[SUP]1[/SUP], Burns A[SUP]1[/SUP], Stablein C[SUP]1[/SUP], Wolff M[SUP]1[/SUP], Jolles B[SUP]1[/SUP], Leung B[SUP]1[/SUP], Lambert L[SUP]1[/SUP], Shorer S[SUP]1[/SUP], Buchanan W[SUP]1[/SUP], Murray S[SUP]1[/SUP], Chang S[SUP]1[/SUP], Gorman R[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs.
[h=4]METHODS:[/h] A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant. Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18-49 years.
[h=4]RESULTS:[/h] Two hundred and seventy subjects were enrolled. After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001). Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher. Vaccine + MF59 produced cross-reactive antibody responses against 4 heterologous H5N1 viruses. Excellent safety and tolerability were demonstrated.
[h=4]CONCLUSIONS:[/h] Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe. The feasibility of the point-of-use mixing should be studied further.
[h=4]KEYWORDS:[/h] H5N1; MF59; adjuvant; antibody; avian influenza; pandemic preparedness; point-of-use mixing; vaccine
PMID: 25734170 [PubMed] PMCID: PMC4324215 Free PMC Article