A Cell Culture (Vero)–Derived H5N1 Whole‐Virus Vaccine Induces Cross‐Reactive Memory Responses

Abstract

Novel strategies are required to provide rapid vaccine coverage in the event of an influenza pandemic. A phase I/II dose finding/formulation study was performed with a whole-virus H5N1 clade 1 A/Vietnam vaccine (2-dose priming regimen) to evaluate safety and immunogenicity. Seventy-seven of 141 subjects in this study received a booster (12-17 months after priming) with a 7.5-microg dose of a clade 2.1 A/Indonesia vaccine. The prime-boost regimen resulted in antibody responses against clade 1, 2.1, 2.2, and 2.3 viruses that were significantly higher than those after the priming regimen. These findings demonstrate that a prime-boost regimen may alleviate vaccine supply constraints in a pandemic.

Enhanced Growth of Influenza Vaccine Seed Viruses in Vero Cells Mediated by Broadening the Optimal pH Range for Virus Membrane Fusion

“…Presently, cell culture-based inactivated influenza vaccines are in clinical trials or have been approved for use in some countries (1,7,8,13,19). This approach has considerable advantages over egg-based vaccines because (i) it can lead to more rapid and larger-scale vaccine production (10); (ii) it may avoid the potential for selecting variants adapted for chicken eggs, which alters virus antigenicity (18); (iii) selection of high-yield vaccine seed viruses is needed for egg-based production; and (iv) it does not contain allergic components of eggs (16).…”

New technologies for influenza vaccines

“…4 [5][6][7][8][9][10][11][12][13][14][15] There are pre-clinical reasons to believe that improvements to the vaccine seed virus generation process could lead to clinical improvements in cell culture-based vaccines.…”

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

“…67,69,71,72 Seroprotective levels of antibodies were achieved in 10-100% of the individuals, generally mirroring the variation observed in seroconversion. [67][68][69][70][71][72] In general, SRP levels were observed in >70% of the subjects after 2 conventional doses, and the proportion of subjects rose to >90% of the adults and >70% of the elderly following another dose at 6, 12-15 or 24 months following a single or a double dose administered earlier. 70 GMRs ranging from 1.6 to 32.8 have been observed, again following a pattern similar to SRC and SRP.…”

“…66 Human clinical trials for Vero cell-derived A/H5N1 influenza vaccines showed that doses ranging from 3.75 to 45 mg of hemagglutinin (HA) protein equivalent were well tolerated, induced robust clade-and cross-clade-reactive antibodies in pediatric and adult populations, and that these responses could be boosted 6-24 months later. [67][68][69][70][71][72] Seroconversion rates ranged from 6% to 86%; the responses were typically higher with a higher dose or following boosting, but lower when adjuvanted with aluminum salts, in older individuals, and against viruses belonging to heterologous clades. Significantly, responses persisted for 12-24 months in a considerable proportion (26-86%) of the subjects.…”

“…67,70,71,79 The most frequently reported local AEs have been pain at injection site (10-43% of the subjects), followed by redness, swelling, induration and ecchymosis. 67,70,71,[79][80][81] Total systemic AEs have been reported in 18-51% of the subjects, 65,68,69 the most common being headache, fatigue, myalgia and malaise (3-20% of the subjects) in adults as well as the elderly. 70,71,81 A wider variety of events have been reported in children.…”