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https://www.arca.fiocruz.br/handle/icict/63912
THERMAL STABILITY EVALUATION OF A CHIMERIC LIVE-ATTENUATED ZIKV VACCINE CANDIDATE USING DIFFERENT STABILIZERS IN FORMULATION
Author
Affilliation
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
xmlui.dri2xhtml.METS-1.0.item-abstractes
Introduction: After eight years of Zika outbreak in Brazil, no vaccine has already been approved.
The stability study is one of the most important steps for new vaccines development, as well as new
formulations, ensuring the maintenance of product quality, safety, and efficacy throughout the shelf-life.
Objectives: So, this study aimed to evaluate the effect of excipients in different concentrations on the
thermal stability of a chimeric live-attenuated Zika virus (ZIKV) vaccine to define the best formulation
to be freeze-dried.
Methodology: After purification, chimeric ZIKV, produced with two concentrations of recombinant
human serum albumin (rHSA), was submitted to different temperatures (2-8°C, 25°C, 37°C) for 0-14
days.
Results: It was observed that virus titers are more variable at highest temperatures. Nevertheless, the
difference in residual rHSA concentration between the batches tested, 2.68–0.005 mg/mL, does not interfere
in virus stability. Though, chimeric ZIKV was diluted to 103
, 104
and 105
FFU/dose, no stabilizers, and
incubated at 2- 8°C. After 4 h, the viral titer was reduced by 0.6 log to non-detectable levels (according to
the test LOD), especially in most diluted conditions. Therewith, chimeric ZIKV was formulated with 105
FFU/dose using stabilizing excipients, generating F1, F2 and F3 solutions (minor, intermediate and major
concentrations). The potency of formulated vaccines was investigated by accelerated stability assay, as
previously described. It could be observed, for all tested formulations, a drop in vaccine titer from day
3 onwards, at 25°C and 37°C, excepted for control (FC), not formulated, which already loses stability at
day 0. Among all tested formulations, F1 was the less stable one, losing up to 0.5-1 log FFU. Conversely,
solutions F2 and F3 maintained virus stability for at least 14 days at 2-8°C. As expected, viral titers
decreased as the temperature increased.
Conclusion: So, these results suggest that F2 and F3 are promising formulations to be used in the future
freeze- drying tests of the ZIKV vaccine candidate. Accelerated stability tests will be repeated with the
freeze-dried vaccine to determine thermal stability profile that ensures quality delivery at the point of care.
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