Immunogenicity and Safety of an EB66 Cell-Culture-Derived Influenza A/Indonesia/5/2005(H5N1) AS03-Adjuvanted Vaccine: A Phase 1 Randomized Trial.
BACKGROUND
Cell-culture-derived (CC) influenza vaccine production methods could provide benefits over classical embryonated-egg technology, including a higher production capacity and the faster creation of a supply that meets demand.


METHODS
A CC-inactivated split-virus influenza A/Indonesia/5/2005(H5N1) vaccine derived from the EB66 cell line (hereafter, "CC-H5N1") was investigated in a phase 1 randomized, blinded study. Healthy adults (n = 521) received 2 vaccine doses (days 0 and 21) of either investigational CC-H5N1 vaccine (1.9 µg or 3.75 µg of hemagglutinin antigen [HA] with the AS03 adjuvant system or 15 µg of plain HA), embryonated-egg-derived vaccines (3.75 µg of HA with AS03 or 15 µg of plain HA), or placebo. Assessment of the adjuvant effect and immunogenicity was performed using Center for Biologics Evaluation and Research acceptability criteria 21 days after dose 2. Safety was assessed until month 12.


RESULTS
AS03-adjuvanted CC-H5N1 elicited a homologous hemagglutination inhibition antibody response that satisfied immunogenicity criteria 21 days after dose 2 and persisted at month 12. Adjuvant effect and immune response against a drift-variant strain were demonstrated. No vaccine-related serious adverse events were reported. The immunogenicity and safety of the CC-H5N1 formulation containing 3.75 µg of HA and AS03 appeared to be similar to those for the licensed egg-derived AS03-adjuvanted control vaccine.


CONCLUSIONS
The feasibility of the EB66 cell line to produce an immunogenic influenza vaccine with acceptable safety profile was demonstrated. Antigen sparing was achieved through combination with AS03 adjuvant. This CC-H5N1 might contribute to the rapid access of vaccine in the event of an influenza A(H5N1) pandemic.


BACKGROUND
NCT01236040.
GSK Vaccines, King of Prussia, Pennsylvania.
Anne
A
Schuind
Clinical Research Atlanta, Stockbridge, Georgia.
Nathan
N
Segall
GSK Vaccines, King of Prussia, Pennsylvania.
Mamadou
M
Drame
GSK Vaccines, King of Prussia, Pennsylvania.
Bruce L
BL
Innis
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D004338:Drug Combinations; D004372:Ducks / Q000196:embryology; D053595:Embryonic Stem Cells; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000009:adverse effects / Q000494:pharmacology*; D016037:Single-Blind Method; D013185:Squalene / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult; D024502:alpha-Tocopherol / Q000009:adverse effects / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
AS03; cell culture; influenza A(H5N1); pandemic influenza vaccine