Cell culture-derived flu vaccine: Present and future

Rubio, Alberto Pérez; Eiros, José María

doi:10.1080/21645515.2018.1460297

Cited by 55 publications

(38 citation statements)

References 75 publications

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“…Although the egg-based production platform is the major supply of seasonal influenza vaccines, the vulnerable chain for the egg supply raises a concern of vaccine supply during pandemics. In addition, low clinical effectiveness of recent egg-derived H3N2 vaccines further demonstrates the urgent need of alternative production platforms, such as cell-based and recombinant protein-based platforms [ 19 ]. As discussed previously, the Vero cell-based multifunctional platform is potentially valuable for influenza pandemic preparedness [ 4 ], but this platform also needs high-growth MDVs to increase productivity.…”

Section: Discussionmentioning

confidence: 99%

Development and Evaluation of Vero Cell-Derived Master Donor Viruses for Influenza Pandemic Preparedness

Chen

Tzeng

et al. 2020

Vaccines

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The embryonated egg-based platform currently produces the majority of seasonal influenza vaccines by employing a well-developed master donor virus (MDV, A/PR/8/34 (PR8)) to generate high-growth reassortants (HGRs) for A/H1N1 and A/H3N2 subtypes. Although the egg-based platform can supply enough seasonal influenza vaccines, it cannot meet surging demands during influenza pandemics. Therefore, multi-purpose platforms are desirable for pandemic preparedness. The Vero cell-based production platform is widely used for human vaccines and could be a potential multi-purpose platform for pandemic influenza vaccines. However, many wild-type and egg-derived influenza viruses cannot grow efficiently in Vero cells. Therefore, it is critical to develop Vero cell-derived high-growth MDVs for pandemic preparedness. In this study, we evaluated two in-house MDVs (Vero-15 and VB5) and two external MDVs (PR8 and PR8-HY) to generate Vero cell-derived HGRs for five avian influenza viruses (AIVs) with pandemic potentials (H5N1 clade 2.3.4, H5N1 clade 2.3.2.1, American-lineage H5N2, H7N9 first wave and H7N9 fifth wave). Overall, no single MDV could generate HGRs for all five AIVs, but this goal could be achieved by employing two in-house MDVs (vB5 and Vero-15). In immunization studies, mice received two doses of Vero cell-derived inactivated H5N1 and H7N9 whole virus antigens adjuvanted with alum and developed robust antibody responses.

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Section: Discussionmentioning

confidence: 99%

Development and Evaluation of Vero Cell-Derived Master Donor Viruses for Influenza Pandemic Preparedness

Chen

Tzeng

et al. 2020

Vaccines

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“…The culturing of IAV from wild, non-avian hosts in embryonated chicken eggs (ECE) is a known challenge in the influenza field. Recent seasonal H3N2 viruses from humans have proven difficult to propagate in ECEs (Donis et al, 2014;Perez-Rubio and Eiros Bouza, 2018) and attempts to grow IAVs from marine mammals in ECEs are often unsuccessful (Puryear et al, 2016;Davis et al, in preparation). Propagation in chicken eggs depends upon the receptor binding affinity, fusion, and budding of the virus in ECEs, the concentration of virus, and the combination of both.…”

Section: Discussionmentioning

confidence: 99%

“…Propagation in chicken eggs depends upon the receptor binding affinity, fusion, and budding of the virus in ECEs, the concentration of virus, and the combination of both. While further passages in ECEs can result in viral isolation, using mammalian epithelial cell culture lines, such as MDCK cells, VERO cells, or in this case rat-derived epithelial cells may be beneficial in isolating and amplifying sufficient amounts of virus to be adequately sequenced (Donis et al, 2014;Perez-Rubio and Eiros Bouza, 2018). While it is unclear if rats are infected with IAV based exclusively on the molecular data presented here, the presence of viral nucleic acid in samples collected from the study population across field seasons and multiple swab sites is suggestive of replication within rats and transmission between conspecifics.…”

Section: Discussionmentioning

confidence: 99%

Evidence of Influenza A in Wild Norway Rats (Rattus norvegicus) in Boston, Massachusetts

et al. 2019

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Influenza A virus (IAV) is known to circulate among human and animal reservoirs, yet there are few studies that address the potential for urban rodents to carry and shed IAV. Rodents are often used as influenza models in the lab, but the few field studies that have looked for evidence of IAV in rodents have done so primarily in rural areas following outbreaks of IAV in poultry. This study sought to assess the prevalence of IAV recovered from wild Norway rats in a dense urban location (Boston). To do this, we sampled the oronasal cavity, paws, and lungs of Norway rats trapped by the City of Boston's Inspectional Services from December 2016 to September 2018. All samples were screened by real-time, reverse transcriptase PCR targeting the conserved IAV matrix segment. A total of 163 rats were trapped, 18 of which (11.04%) were RT-PCR positive for IAV in either oronasal swabs (9), paw swabs (9), both (2), or lung homogenates (2). A generalized linear model indicated that month and geographic location were correlated with IAV-positive PCR status of rats. A seasonal trend in IAV-PCR status was observed with the highest prevalence occurring in the winter months (December-January) followed by a decline over the course of the year, reaching its lowest prevalence in September. Sex and weight of rats were not significantly associated with IAV-PCR status, suggesting that rodent demography is not a primary driver of infection. This pilot study provides evidence of the need to further investigate the role that wild rats may play as reservoirs or mechanical vectors for IAV circulation in urban environments across seasons.

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“…The ten strategies included in this analysis are presented in Table 1 . The different vaccines considered are quadrivalent influenza vaccine [QIV] [ 16 ], recombinant QIV [ 17 ], trivalent influenza vaccine [TIV] [ 18 ], TIV-high dose [HD] [ 19 ], QIV cell culture-derived [ 20 ], and adjuvanted TIV [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Constrained Optimization for the Selection of Influenza Vaccines to Maximize the Population Benefit: A Demonstration Project

Standaert

Vlaenderen

Bellinghen

et al. 2019

Appl Health Econ Health Policy

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Background Influenza is an infectious disease causing a high annual economic and public health burden. The most efficient management of the disease is through prevention with vaccination. Many influenza vaccines are available, with varying efficacy and cost, targeting different age groups. Therefore, strategic decision-making about which vaccine to deliver to whom is warranted to improve efficiency. Objective We present the use of a constrained optimization (CO) model to evaluate targeted strategies for providing influenza vaccines in three adult age groups in the USA. Methods CO was considered for identifying an influenza vaccine provision strategy that maximizes the benefits at constrained annual budgets, by prioritizing vaccines based on return on investment. The approach optimizes a set of predefined outcome measures over several years resulting from an increasing investment using the best combination of influenza vaccines. Results Results indicate the importance of understanding the relative differences in benefits for each vaccine type within and across age groups. Scenario and threshold analyses demonstrate the impact of changing budget distribution over time, price setting per vaccine type, and selection of outcome measure to optimize. Conclusion Significant gains in cost efficiency can be realized for a decision maker using a CO model, especially for a disease like influenza with many vaccine options. Testing the model under different scenarios offers powerful insights into maximum achievable benefit overall and per age group within the predefined constraints of a vaccine budget. Electronic supplementary material The online version of this article (10.1007/s40258-019-00534-y) contains supplementary material, which is available to authorized users.

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Cell culture-derived flu vaccine: Present and future

Cited by 55 publications

References 75 publications

Development and Evaluation of Vero Cell-Derived Master Donor Viruses for Influenza Pandemic Preparedness

Development and Evaluation of Vero Cell-Derived Master Donor Viruses for Influenza Pandemic Preparedness

Evidence of Influenza A in Wild Norway Rats (Rattus norvegicus) in Boston, Massachusetts

Constrained Optimization for the Selection of Influenza Vaccines to Maximize the Population Benefit: A Demonstration Project

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