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Research Article - (2016) Volume 7, Issue 3

Cross-Sectoral Perspectives of Market Implementation of the MVA Platform for Influenza Vaccines: Regulatory, Industry and Academia

Bahar Ramezanpour1*, Osterhaus A2,3 and Claassen E1
1Vrije Universiteit Amsterdam, Earth & Life Sciences, Athena Institute, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands, E-mail: [email protected]
2University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany, E-mail: [email protected]
3Artemis One Health Research Foundation, Androclus Building, Uithof Yalelaan 1, 3584 CL Utrecht, The Netherlands, E-mail: [email protected]
*Corresponding Author: Bahar Ramezanpour, Vrije Universiteit Amsterdam, Earth & Life Sciences, Athena Institute, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands, Tel: +31-611957039 Email:

Abstract

This study provides a quantitative multidisciplinary approach to identify and prioritize the main implementation challenges of the MVA platform for novel influenza vaccines using a tailor-made prioritization process. Influential key opinion leaders (KOL’s) in the field of vaccine research, development, and manufacturing were approached to participate in this study. Semi-structured interviews were performed with 32 KOL’s representing the regulatory, industry, and academia fields.

The opinions were analyzed quantitatively, through various ranking methods that were integrated and adapted to fit the purpose of this study, identifying 6 implementation challenges main categories, 21 implementation challenges categories, and 39 implementation challenges underlying causes. The most significant barriers are associated with “production & speed” category whereas the least significant are associated with “regulatory” category.

Perspectives among the KOL’s proved to be divergent with regard to implementation challenges for the MVA platform. Through comparing these perspectives, useful information on current and potential future implementation challenges of novel platforms in general may be expected. Providing an overview and assessment to reveal these challenges may lead to a more substantial situation for all stakeholders involved, given that such an overview allows for the recognition of various implementation challenges from a multidisciplinary perspective, making it possible to identify underlying causes that contribute to the successful implementation of the MVA platform. Remarkably, analysis of implementation challenges resulted in core challenges that resemble similarities between the three perspectives.

Keywords: MVA platform; Market implementation; Novel technologies; Novel platforms; Vaccine industry; Interdisciplinary perspectives; Influenza vaccines

Introduction

Despite the success of vaccines in disease prevention and control [1], vaccination still has the potential to make an even greater contribution to public health on a global scale [2]. Introduction of recent advances and novel approaches in the influenza vaccine field provide new opportunities that emphasize the need for adapting/ improving state-of-the-art technologies.

With a global annual attack rate estimated at 5%-10% in adults and 20%-30% in children, influenza viruses continue to emerge and reemerge causing approximately 3 to 5 million cases of severe illness, and 250 000 to 500 000 deaths annually [3]. Immunization remains the most effective way to prevent or mitigate influenza [4].

Although current annual influenza vaccines are relatively effective against epidemic influenza infections, these vaccines don’t provide protection against pandemic and emerging influenza viruses [5]. Moreover, ensuring an adequate and timely supply of vaccines remains challenging due to, inter alia, the limitations of current technologies [4,6-9]. For the production of influenza vaccines, egg-based and egg-independent technologies are being used [10]. Even though many benefits arrive from egg-based influenza vaccine production, there are several essential disadvantages. Up scaling of production to meet the global demand is limited by embryonated chicken egg supplying mechanisms. This can also be affected by the virulence of pandemic strain since these viruses can be lethal to embryonated chicken eggs [4]. Moreover, an increased surge in vaccine demand during a pandemic will generate at least 5-10 fold of the current global seasonal influenza vaccine production demand [10].

Egg-independent pandemic influenza vaccine approaches include, but are not limited to, cell-derived whole or detergent split, recombinant proteins, virus-like particles, DNA/RNA vaccines, and viral vector vaccines [10-13]. While all these technologies have inherent potential to improve influenza vaccines by increasing production capability and providing shorter production time, many are limited by efficacy and safety concerns. Recent research shows the promise of using viral vector vaccines with certain additional assets, including ability to induce balanced humoral and cellular immune responses and feasibility for large-scale deployment in a short period of time without the safety concerns associated with the production of pathogenic viruses [4,10,14-17].

In recent decades recombinant poxviruses have shown potential as platforms for the development of vaccines that induce protective immunity against various infectious and neoplastic conditions of humans and animals with a good safety profile [18,19]. The latter is probably due to their replication, which is largely restricted to avian cells. Despite the availability of a series of attenuated poxviral vaccine vectors with a good safety profile, modified vaccinia virus Ankara (MVA) is among the most advanced and widely used attenuated vectors in clinical trials [20,21].

In our previous study, we have quantified the strengths, weaknesses, opportunities, and threats that come with the modified vaccinia virus Ankara (MVA) platform [7]. Here we present implementation challenges of this platform. Furthermore, although different vaccinia virus vectors are being used in many clinical trials against various diseases, such as HIV [22-24], hepatitis [25], influenza [26], malaria [27,28], tuberculosis (TB) [29], and cancer [30,31], MVA vectors have proven to be relatively safe as compared to other vaccinia virus strains [32,33].

An increasing number of novel development/production approaches including viral vector-based techniques shows its potential added value to develop new vaccines that address an unmet medical need. Nonetheless, lack of proper rules and regulations and stringent regulatory requirements act as obstacles in bringing a vaccine candidate to the clinic [34]. International and national regulatory agencies require stringent experiments to address concerns regarding the introduction of novel vaccines. The present study shows that involvement of regulatory, industry, and academia worlds contributes to streamline and improve required regulations, possible biosafety issues, and MVA-vector-associated risks.

The vaccine licensure process prior to vaccine approvals plays a decisive role for manufacturers to expand their engagement in development and manufacturing of novel vaccines [35]. Although demonstration of added value of novel generation vaccines contributes to their successful registration and implementation on the market, providing convincing clinical data appears to be challenging for manufacturers [4]. Furthermore, dependency on external factors discourages industry to invest in development of novel vaccines.

In the present study, we uncover market implementation challenges of the MVA platform [7] by performing semi-structured interviews with the KOL’s representing the golden triad; regulatory, industry, and academia. Quantifying expert’s opinions regarding market implementation challenges of the MVA platform through various ranking methods (integrated assessment (IA) approach, perspective method, and rank-frequency and importance frequency methods) provides a unique overview from a multidisciplinary perspective, making it possible to identify foremost underlying causes that contribute to the challenges novel vaccines have to face before successful market implementation.

Methodology

A comprehensive analysis of our previous study indicated the added value of diverse perspectives that exist among the KOL’s with different backgrounds [7]. A multidisciplinary approach has been used to represent the most influential stakeholders in the field of vaccine research, development, and manufacturing, namely; regulatory, industry, and academia.

Data collection consisted of a literature study on the topic of this research and interviews with KOL’s. Semi-structured qualitative interviews serve as a tool to further identify the main implementation challenges in the field of influenza vaccine [36]. The prioritization process was based on several quantitative ranking methods that were integrated and adapted to fit the purpose of our research; integrated assessment (IA) approach [37-42], perspectives method [43,44], and rank-frequency and importance frequency methods [45,46]. The results from all analyses are integrated to create a RCA tree [47,48] (RCA applied top-down) visualizing all three perspectives (Table 1).

vaccines-vaccination-study-design

Table 1: Study design.

Descriptive study design

Root cause analysis (RCA): Root cause analysis is an approach designed to identify the underlying causes of events, in this case MVA implementation challenges on the influenza market. Identification of underlying causes enables to reveal different effective options for solutions. The RCA is a four-step process including data collection, causal factor visualization, root cause identification, and generation of the most effective recommendation to overcome the challenges [49,50].

Interviews: The interview candidates were purposively selected using the snowball method [50,51] to provide a diverse and complete overview from the field of influenza. The interviewees were asked a standardized set of questions in order to make the results comparable. The results from the interviews were subsequently used for further analysis (Table 2).

Background Interviewees Response rate
Regulatory 9 23%
Industry 18 100%
Academia 5 39%
Total 32 48%

Table 2: Interviewee’s background.

Integrated assessment (IA) approach: Integrated assessment (IA) approach provides the opportunity to integrate knowledge and perspectives from several domains into a single framework. This research approach pursues scientific understanding of complex issues based on combining, interpreting, and communicating knowledge from different disciplines in such way that a cause-effect chain of an issue can be evaluated from different perspectives [37-42]. In contrary to conventional research analysis, IA is very effective in not only unveiling problems and their underlying causes, but at the same time providing relations between these causes. Complex problems have several causes that sometimes interact across multiple domains, consequently, requiring application of inter- and trans-disciplinary approaches.

Perspective method: Together with the aforementioned approach, the perspectives method focuses on the interaction and interrelation between regulatory, industry, and academia KOL’s in a multidisciplinary way. The perspective method classifies, interprets, and analyses these different perspectives [43,44]. We developed a set of questions and conducted interviews with the KOL’s from the field of influenza as part of the perspectives method to analyse the current perspective on the implementation of MVA platform among the experts with different backgrounds. Subsequently, a dimensional perspective construction was created providing insight into differences and similarities between the three stakeholders. This construction plays an essential role in identification of reasons behind discrepancies and demonstrates inherent challenges at different levels.

Rank-frequency and importance-frequency methods: The rankfrequency method cross-tabulates the frequency of an item with its appearance ranking. This method consists of two indicators: the frequency of a factor and its appearance ranking. The importancefrequency method replaces the appearance ranking criterion with an importance ranking criterion [46].

Results

A total of sixty-two peer-reviewed publications, divided in scientific reviews (12), scientific publications (30), and governmental guidelines (3) were evaluated in order to attain more insight into the topic of this study (Table 3).

Reviews Publications Governmental Guidelines
Altenburg et al. 2014 Andre et al. 2008 Hanton et al.2002 Kaper et al.category “technical” is ranked to posses 2005
Chan et al. 2013 Baarda et al. 2005 Offermans et al. 2012 WHO et al. 2014
Cherp et al. 2011 Bakari et al. 2011 Osterhaus et al. 2011 WHO et al. 2012
Choi et al. 2013 Bejon et al. 2007 Ramezanpour et al. 2015  
Cottingham et al. 2013 Berthoud et al. 2011 Rotmans et al. 1998  
Krammer et al. 2015 Cavenaugh et al. 2011 Schneider et al. 1997  
Lee et al. 2014 Dany et al. 2015 Sheehy et al. 2012  
Mooney et al. 2013 De Ridder et al. 2007 Smits et al. 2009  
Pandey et al. 2010 Draper et al. 2013 Suter et al. 2009  
Perdue et al. 2011 Edenhofer et al. 2005 Tameris et al. 2013  
Rimmelzwaan et al. 2009 Ferenc et al. 2003 Ulmer et al. 2006  
Rollier et al. 2011 Garcia et al. 2011 Valkering et al. 2009  
  Goodman et al.1961 Verheust et al. 2012  
  Gomez et al. 2011 Verschuren et al. 2010  
  Greenwood et al. 2011 Zeng et al. 2014  

Table 3: List of total evaluated reviews, publications, and governmental guidelines.

Policy making on implementation of a vaccine development/ production platform involves diverse fields of expertise. To assess the MVA market implementation challenges under different perspectives, 30 KOL’s from the vaccine field were interviewed. As a result, three distinctive perspectives on implementation of MVA platform emerged, each led by its own established view in a different discipline and each with a predominant emphasis on specific set of underlying causes (Figure 2). The analysis of interview transcripts reveals 6 main categories of implementation challenge, which subsequently are divided into 21 categories of implementation challenges. These categories are further subdivided into 39 underlying causes.

Dimensional perspective construction; three perspectives, their similarities and differences

Mapping the implementation challenges in a dimensional perspective construction visualizes differences and similarities between KOL’s responses (Figure 1). This figure illustrates the core implementation concerns associated with each perspective. According to the KOL’s multidisciplinary perspectives, following implementation categories are ranked as top three and thus are essential: challenging to provide convincing clinical data, external dependency, and need for new production platforms/facilities. Furthermore, analysis of the obtained data made it possible to identify several other important categories by KOL’s perspectives: flexibility requirements, regulatory construct, licensable vaccines, and challenging to demonstrated efficacy, respectively (Figure 1).

vaccines-vaccination-Dimensional-perspective

Figure 1: Dimensional perspective construction. Three perspectives on MVA platform implementation have their roots in separate disciplines; regulatory, industry, and academia. They differ with respect to their focus on various domains. The implementationchallenge- categories are situated in the centre of the diagram address the concerns of all three perspectives. Each additional layer represents a different perspective illustrated by colour. And each colour represents a separate main category of implementation challenges. The outer shell represents the main KOL’s perspective.

From the regulatory, industry, and academia perspective, it is challenging to demonstrate efficacy in clinical trials and therefore difficult to provide compelling data. According to the KOL’s, external dependency on factors such as strain reference and reagents emphases the necessity for new production platforms/facilities, which consequently contribute to a more rapid production process and hopefully translating to faster market entry. Flexibility is a prerequisite in every step of the process in order to eventually produce licensable vaccines and acquire regulatory approval.

According to the KOL’s from the regulatory authorities and industry, influenza market is viable, large, and complex. Industry emphasizes the importance of demonstrating added value of a product in comparison to other competitive products. Providing compelling data is necessary to validate this added value and make a product more appealing to the eyes of different stakeholders. Moreover, an extensive intellectual property (IP) profile is a requirement in this field.

According to the regulatory authorities, providing knowledge and quantitative assessments might be one of the most essential compelling factors helping the acceptance of MVA platform by various stakeholders including public, politicians, and governments. From the academia perspective, the effects of pre-existing immunity against vaccine vectors in the human population may represent a barrier in successful implementation of such platforms. Furthermore, public acceptance towards vector-based vaccines is one of the profound challenges in successful market implementation of MVA.

Both regulatory and academia KOL’s indicate that the industry needs to be incentivized to make further investments in the development of novel technologies. Complex territorial regulations and requirements complicate translating vaccine candidates into actual vaccines. Furthermore, implementation of MVA platform might interfere with ongoing projects in the pipeline. A good business model is required to ensure application sustainability of this platform, from an industry perspective. Application of an advance-purchaseagreement-purchaseagreement can support sustainability and helps risk sharing for development of pandemic vaccines.

RCA tree

Implementation challenges of the MVA platform are assigned to six main categories: production and speed, technical, immunogenicity, competitors, pre-pandemic/ mock-up, and regulatory. These categories are further classified and ranked according to their importance into 21 implementation challenges categories. Underlying causes, a total of 39, related to each challenge are also illustrated in Figure 2.

vaccines-vaccination-RCA-tree-Integration

Figure 2: RCA tree. Integration of the overall results: root-cause analysis (RCA), rank-frequency method, integrated assessment (IA) approach, and perspectives method of MVA platform implementation.

Production and speed: Comparing to other implementation main categories, the main category “production & speed” has the highest overall score. External dependency challenges, posed predominantly by industry KOL’s, are a predominant implementation challenge of the MVA platform. The foremost underlying causes for delay in the production process are unpredictable global demands, external factor including reagents and reference strains provided by the WHO, and rules & regulations. Moreover, advanced production platforms and proper facilities are required to speed-up the process of market entry and validation.

Technical: The main category “technical” is ranked to possess the second highest scores. Within this category flexibility requirements to match antigenic changes in circulating viruses are ought to be essential. Nevertheless, lack of knowledge to provide quantitative assessments regarding cross-reactivity and required protection immunity remains a challenge. Consequently, technical challenges and unpredictable market dynamics and demands are considered to be of high risk to manufacturers when deciding to invest in novel technologies.

Immunogenicity: Within this main category, challenges related to provide convincing clinical data are the foremost mentioned challenge, in particular from a regulatory perspective. The main underlying causes are the lack of clinical data on immunogenicity, crossprotection, safety, and efficacy. Additionally, comparison to the current standard of care raises the bar even higher (Figure 2).

Competitors: Due to the large and complex nature of the influenza market and many comparable competitive products available in late stage development, demonstrating added value assures competitive advantages in gaining market share and public acceptance. Furthermore, the public needs to be educated on the value of vaccinating with a virus, MVA, against another virus, influenza.

Pandemic/Mock-up: Mock-up dossiers are regulatory constructs to make advance-purchase-agreements with governments due to unattractive nature of pandemic vaccines during peacetime. Moreover, mock-up vaccines facilitate and increase the chance of getting proof of concept vaccines into clinical trials. This business strategy will ensure sustainability and therefore increase the chance for development of licensable vaccines by the industry.

Regulatory: According to the regulatory authorities, lack of incentives for vaccine manufacturers and complex requirements and regulations for novel vaccines complicates the translation of pandemic candidates into actual vaccines.

Importance frequency

Results presented here indicate the most important implementation challenges, main categories/ categories/ underlying causes, ranked according to each perspective (Figure 3).

vaccines-vaccination-Importance-frequency-ordered

Figure 3: Importance frequency, ordered according to all results of implementation challenges categories from the regulatory, industry, and academia perspective.

From the perspective of the regulatory authority and academia KOL’s, providing convincing clinical data with the purpose of vaccine approval remains the most challenging factor for the implementation process of MVA platform. External dependency is experienced as the most essential implementation barrier that the industry has to face in order to get the MVA vaccine development/production platform on the market. All three perspectives consider these challenges as predominant barriers, however with variable importance degrees depending on their backgrounds.

There are also some implementation-challenge-categories solely mentioned by one perspective. Regulatory authorities indicate public/ politicians/governments acceptance to play an essential role in the future after implementation of this platform. According to the industry KOL’s, sustainability of such platform with respect to time-bound properties of these pandemic vaccines and importance of having a solid business strategy to remain successful is going to be a profound challenge. From the perspective of the academia KOL’s, public acceptance of such platform must also be taken into consideration while discussing the challenges.

Discussion/Conclusion

The current study evaluates the market implementation potential of MVA platform to generate next-generation influenza vaccines, which will provide superior immunogenicity, safety profile, and shorter production time. Our study reveals that implementation barriers of the MVA platform can be grouped into six main categories (ranked according to importance): “production & speed”; “technical”; “immunogenicity”; “competitors”; “pre-pandemic/mock-up” and “regulatory”. It is noteworthy that the top three categories when ranked according to the rank-frequency as well as that importance frequency coincides with the top three categories shared by all three perspectives. Approaching KOL’s representing industry, regulatory, and academia shows how complex the acceptance of an MVA based influenza vaccine production platform can be.

Visualization of integrated results shows that dependency on external factors such as reagents and reference strains requires immediate attention based on the fact that this category is related to the most important main category, “production & speed”. Regulatory and academia commonly recommend making less complex and more streamlined regulations that consequently will, inter alia, incentivize the manufacturers to develop vaccines instead of vaccine candidates (Figure 2). Therefore, it is noteworthy that the main category “regulatory” is not as highly ranked as it is generally assumed to be [51]. This state of discrepancy between KOL’s perspectives highlights ambiguity regarding novel vaccines regulations and stresses the need for custom-made rules, regulations, and guidelines.

At present, many of the core implementation challenges overlap between the three perspectives with a remarkably high level of resemblance on required immediate attention for the top two challenges. This not only reveals that the solution to these challenges must be an integrated effort, but it also emphasizes the importance of breaking the barriers by working together. This new way of collaboration between various stakeholders will eventually redefine their relationship.

High level of urgency for new production platforms/facilities requires speeding up the search for novel platforms that meet the requirements. Consideration of combining novel technologies with conventional production platforms and vaccine formulations is necessary to speed up the production of vaccines and reduce time gap between the emergence of new influenza viruses and vaccine availability.

Successful introduction and registration of a new vaccine (platform) is based on and influenced by various factors including provision of sufficient information to decision makers, demonstration of added value comparing to existing products, increased public acceptance of the vaccines by demonstrating safety, efficacy, sustainability, and costeffective.

Industry KOL’s indicate establishing a sustainable business model as a prerequisite to turn a relative commercially unattractive platform into a success. Depending on market dynamics and uncertainties, manufacturers can be confronted with various unexpected events, such as technological/developmental failures and technological/logistical and regulatory challenges, which all contribute to the risks manufacturers have to face in order to realize developing novel pandemic vaccines [8]. Nevertheless, this study indicates that datadriven decision-making for vaccine development approaches will provide a dominating competitive advantage in this large and viable market.

Providing compelling data representing added value of novel technologies and demonstrating competitive edge to many existing products on the market is deemed very important both by regulatory and industry KOL’s. Hence, it is essential to explore application of this platform for both seasonal and pandemic influenza as well as other infectious diseases [7]. Moreover, alternative route of immunization such as oral, needle-free skin delivery, nasal, and sublingual must be considered as well [8].

Furthermore, integration of different perceptions and collaboration of different stakeholders working with different paradigms offering different insights contribute in beneficial decision making and helps reaching consensus when interactive complexity plays a predominant role. First and foremost the clinical data on safety and efficacy must be beyond doubt but public opinion can also be a barrier. Therefore, public attitude and public acceptance towards vector-based vaccines such as MVA is another challenge that must be surmounted aided by the application of clear guidance and regulations by relevant authorities. Moreover, the public needs to be educated on the value of vaccinating with a virus, MVA, against another virus, influenza.

Finally, practical challenges of establishing MVA platform on the market and ensuring effective long-term sustainability of this platform require collaboration from different stakeholders. Our study indicates that once regulatory, industry, and academia fields understand each other’s perspective and come to the realization that they jointly can anticipate market implementation barriers in a collaborative manner that will lead to a strategic dialogue and consequently increased chance of reaching a consensus. This will be beneficial for each and every party involved and will further make an enormous contribution not only to public health but also to the economy.

The future of vaccines is unpredictable due to, inter alia, high complexity, uncertainty, and ambiguity of its market dynamics. In such an uncertain situation, the threats such as regulatory and political fluctuations, innovative and disruptive technologies, and unforeseeable economical and social consequences could be simultaneously barriers and advantages. Identifying, analyzing, quantifying, prioritizing of implementation challenges from different perspectives provide the opportunity to explore different views, evaluate various options, minimize inherently uncertain risks and barriers, consequently anticipate future challenges and be prepared for future threats.

Acknowledgements

This research was financially supported by the European Union FP7 funded-project number 103972 (FLUNIVAC) the European Research Council (ERC) Grant (ARCAS) (2012; Grant No. 324634) [52].

Conflict of Interest

All authors state having no conflict of interest for the conduction of this study.

References

  1. Andre FE, Booy R, Bock HL, Clemens J, Datta SK, et al. (2008)Vaccination greatly reduces disease, disability, death and inequity worldwide. Bull World Health Organ 86: 140-146.
  2. Greenwood B, Salisbury D, Hill AV (2011) Vaccines and global health. Philos Trans R SocLond B BiolSci 366: 2733-2742.
  3. Mooney AJ, Tompkins SM (2013) Experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses. Future Virol 8: 25-41.
  4. Osterhaus A, Fouchier R, Rimmelzwaan G (2011) Towards universal influenza vaccines? Philos transactions of the Royal Society of London Series B. Biological sciences 366: 2766-2773.
  5. Krammer F, Palese P (2015) Advances in the development of influenza virus vaccines. Nat Rev Drug Discov 14: 167-182.
  6. Ramezanpour B, Pronker ES, Kreijtz JH, Osterhaus AD, Claassen E (2015) Market implementation of the MVA platform for pre-pandemic and pandemic influenza vaccines: A quantitative key opinion leader analysis. Vaccine 33: 4349-4358.
  7. Lee YT, Kim KH, Ko EJ, Lee YN, Kim MC, et al. (2014) New vaccines against influenza virus. ClinExp Vaccine Res 3: 12-28.
  8. Rimmelzwaan GF, Sutter G (2009) Candidate influenza vaccines based on recombinant modified vaccinia virus Ankara. Expert Rev Vaccines 8: 447-454.
  9. Pandey A, Singh N, Sambhara S, Mittal SK (2010) Egg-independent vaccine strategies for highly pathogenic H5N1 influenza viruses. Hum Vaccin 6: 178-188.
  10. Perdue ML, Arnold F, Li S, Donabedian A, Cioce V, et al. (2011) The future of cell culture-based influenza vaccine production. Expert Rev Vaccines 10: 1183-1194.
  11. Appavu R, Mohan D, Kakumanu R, Munisamy G (2016) Fundamental of Secondary Structures in Peptide Based Synthetic Nanovaccine Development. Transcriptomics 4.
  12. Rudra JS, Ding Y, Neelakantan H, Ding C, Appavu R, et al. (2016) Suppression of Cocaine-Evoked Hyperactivity by Self-Adjuvanting and Multivalent Peptide Nanofiber Vaccines. ACS ChemNeurosci.
  13. Rollier CS, Reyes-Sandoval A, Cottingham MG, Ewer K, Hill AV (2011) Viral vectors as vaccine platforms: deployment in sight. CurrOpinImmunol 23: 377-382.
  14. Rajagoapl A, Charles BC, Alexey YK, Joshua DS, K FJ, et al. (2015) Enhancing the Magnitude of Antibody Responses through Biomaterial Stereochemistry. ACS Biomaterials Science & Engineering 1: 601-609.
  15. Rajagopal A, Aravinda S, Raghothama S, Shamala N, Balaram P (2012) Aromatic interactions in model peptide β-hairpins: ring current effects on proton chemical shifts. Biopolymers 98: 185-194.
  16. Rajagopal A, Aravinda S, Raghothama S, Shamala N, Balaram P (2011) Chain length effects on helix-hairpin distribution in short peptides with Aib-DAla and Aib-Aib segments. Biopolymers 96: 744-756.
  17. Choi Y, Chang J (2013) Viral vectors for vaccine applications. Clinical and experimental vaccine research 2: 97-105.
  18. Altenburg AF, Kreijtz JHCM, de Vries RD, Song F, Fux R, et al. (2014) Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases. Viruses 6: 2735-2761.
  19. Draper SJ, Cottingham MG, Gilbert SC (2013) Utilizing poxviral vectored vaccines for antibody induction-progress and prospects. Vaccine 31: 4223-4230.
  20. Cottingham MG, Carroll MW (2013) Recombinant MVA vaccines: dispelling the myths. Vaccine 31: 4247-4251.
  21. Gomez CE, Najera JL, Perdiguero B, Garcia-Arriaza J, Sorzano CO, et al. (2011) The HIV/AIDS vaccine candidate MVA-B administered as a single immunogen in humans triggers robust, polyfunctional, and selective effector memory T cell responses to HIV-1 antigens. J virol 85: 11468-11478.
  22. Garcia F, Bernaldo de Quiros JC, Gomez CE, Perdiguero B, Najera JL, et al. (2011) Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02). Vaccine 29: 8309-8316.
  23. Bakari M, Aboud S, Nilsson C, Francis J, Buma D, et al. (2011) Broad and potent immune responses to a low dose intradermal HIV-1 DNA boosted with HIV-1 recombinant MVA among healthy adults in Tanzania. Vaccine 29: 8417-8428.
  24. Cavenaugh JS, Awi D, Mendy M, Hill AV, Whittle H, et al. (2011) Partially randomized, non-blinded trial of DNA and MVA therapeutic vaccines based on hepatitis B virus surface protein for chronic HBV infection. PLoS One 6: e14626.
  25. Berthoud TK, Hamill M, Lillie PJ, Hwenda L, Collins KA, et al. (2011) Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 52: 1-7.
  26. Bejon P, Ogada E, Mwangi T, Milligan P, Lang T, et al. (2007) Extended follow-up following a phase 2b randomized trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS One 2: e707.
  27. Sheehy SH, Duncan CJ, Elias SC, Biswas S, Collins KA, et al. (2012) Phase Ia clinical evaluation of the safety and immunogenicity of the Plasmodium falciparum blood-stage antigen AMA1 in ChAd63 and MVA vaccine vectors. PLoS One 7: e31208.
  28. Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, et al. (2013) Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 381: 1021-1028.
  29. Chan WM, Rahman MM, McFadden G (2013) Oncolyticmyxoma virus: the path to clinic. Vaccine 31: 4252-4258.
  30. Appavu R, Mohan D. Bortezomib in Anti-Cancer Activity: A Potential Drug (2016) Global Journal of Cancer Therapy 2: 005-8.
  31. Verheust C, Goossens M, Pauwels K, Breyer D (2012) Biosafety aspects of modified vaccinia virus Ankara (MVA)-based vectors used for gene therapy or vaccination. Vaccine 30: 2623-2632.
  32. Suter M, Meisinger-Henschel C, Tzatzaris M, Hulsemann V, Lukassen S, et al. (2009) Modified vaccinia Ankara strains with identical coding sequences actually represent complex mixtures of viruses that determine the biological properties of each strain. Vaccine 27: 7442-7450.
  33. Ulmer JB, Valley U, Rappuoli R (2006) Vaccine manufacturing: challenges and solutions. Nat Biotechnol 24: 1377-1383.
  34. WIPO (2012) Patent Landscape Report on Vaccines for Selected Infectious Diseases. France Innovation Scientifique&Transfert.
  35. Baarda DB, De Goede M, Teunissen J (2005) Basisboekkwalitatiefonderzoek: handleidingvoor het opzetten en uitvoeren van kwalitatiefonderzoek. StenfertKroese.
  36. Schneider SH (2005) Integrated assessment of global climate change: Transparent rational tool for policy making or opaque screen hiding value-laden assumptions? Environmental Modelling and Assessment 1997: 229-249.
  37. Edenhofer O, Bauer N, Kriegler E (2005) The Impact of Technological Change on Climate Protection and Welfare: Insights from the Model MIND. Ecological Economics 54: 277-292.
  38. Ferenc L, Toth T, Bruckner HM, Fu¨ssel M, Leimbach G, Petschel-Held (2003) Integrated Assessment of Long-Term Climate Policies: Part I - Model Presentation. Climatic Change 56: 37-56.
  39. Rotmans J (1998) Methods for IA: The challenges and opportunities ahead. Environmental Modeling and Assessment 3:155-179.
  40. De Ridder W, Turnpenny J, Nilsson M, Von Raggamby A (2007) A framework for tool selection and use in Integrated Assessment for Sustainable Development. Journal of Environmental Assessment Policy and Management 9: 423-441.
  41. Valkering P, Tabara D, Wallman P, Offermans A (2009) Modelling Cultural and Behavioural change in Water Management: An integrated, agent based, gaming approach. The Integrated Assessment Journal 9:1-28.
  42. Cherp A, Jewell J (2011) The three perspectives on energy security: intellectual history, disciplinary roots and the potential for integration. Current Opinion in Environmental Sustainability 3: 202-212.
  43. Offermans A (2012) The Perspectives method; towards socially robust river management.
  44. Zeng W, Zeng A, Liu H, Shang MS, Zhou T (2014) Uncovering the information core in recommender systems. Sci Rep 4: 6140.
  45. Dany L, Urdapilleta I, Lo Monaco G (2015) Free associations and social representations: some reflections on rank-frequency and importance-frequency methods. Quality & Quantity 49: 489-507.
  46. Kaper J, Rappuoli R, Buckley M (2005) Vaccine Development: Current Status And Future Needs. American Academy of Microbiology.
  47. Osterhaus ADME (2012) ARCAS: Analysis of the Route to Commercialisation of MVA based influenza vaccines. ARCAS. Erasmus UniversitairMedisch Centrum: European Research Council.
  48. Hanton S, Connaughton D (2002) Perceived control of anxiety and its relationship to self-confidence and performance. Res Q Exerc Sport 73: 87-97.
  49. Smits M, Janssen J, de Vet R, Zwaan L, Timmermans D, et al. (2009) Analysis of unintended events in hospitals: inter-rater reliability of constructing causal trees and classifying root causes. Int J Qual Health Care 21: 292-300.
  50. Goodman LA (1961) Snowball sampling. Annals of Mathematical Statistics 32: 148-170.
  51. Verschuren PJM, Doorewaard H (2010) Designing a Research Project (2nd edn). Eleven International Publishers.
Citation: Ramezanpour B, Osterhaus A, Claassen E (2016) Cross-Sectoral Perspectives of Market Implementation of the MVA Platform for Influenza Vaccines: Regulatory, Industry and Academia. J Vaccines Vaccin 7:318.

Copyright: © 2016 Ramezanpour B, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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