Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza

Chivukula, Sudha; Plitnik, Timothy; Tibbitts, Timothy; Karve, Shrirang; Dias, Anusha; Zhang, Donghui; Goldman, Rebecca; Gopani, Hardip; Khanmohammed, Asad; Sarode, Ashish; Cooper, Dustin L.; Yoon, Heesik; Kim, Young-Hoon; Yan, Yanhua; Mundle, Sophia T.; Groppo, Rachel; Beauvais, Adrien; Zhang, Jinrong; Anosova, Natalie G.; Lai, Charles P.; Li, Lü; Ulinski, Gregory; Piepenhagen, Peter; DiNapoli, Joshua; Kalnin, Kirill; Landolfi, Victoria; Swearingen, Ron; Fu, Tong-Ming; DeRosa, Frank; Casimiro, Danilo R.

doi:10.1038/s41541-021-00420-6

Cited by 67 publications

(51 citation statements)

References 53 publications

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“…Second, several studies demonstrated that combining multiple immune response to different epitopes can increase significantly the efficacy of vaccination [54][55][56][57][58] . The rise of mRNA vaccines 59,60 may facilitate the development of a new generation of multivalent vaccines that could use the pyramiding effect to increase their durability.…”

Section: Discussionmentioning

confidence: 99%

Building pyramids against the evolutionary emergence of pathogens

Gandon

Guillemet

Gatchitch

et al. 2022

Preprint

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Mutations allowing pathogens to escape host immunity promote the spread of infectious diseases in heterogeneous host populations and can lead to major epidemics. Understanding the conditions favoring these evolutionary emergences is key for the development of durable control strategies against pathogens. Here we compare the durability of three different control strategies: (i) a mixing strategy where the host population results from the mix of two single-resistant genotypes, (ii) a pyramiding strategy where host resistance is due to a single double-resistant genotype, (iii) a combining strategy where host resistance is due to a mix between a single-resistant genotype and a double-resistant genotype. First, we use evolutionary epidemiology theory to clarify the interplay between demographic stochasticity and evolutionary dynamics to show that the pyramiding strategy always yields lower probability of evolutionary emergence. Second, we confirm experimentally these predictions using virulent bacteriophages introduced in bacterial populations where we can manipulate the diversity and the depth of CRISPR immunity. Our work shows that pyramiding multiple defenses into the same individual host and avoiding mixing with single-defense strategies is a robust way to protect individuals and populations against pathogen evolutionary emergence. These results have practical implications for the optimal deployment of host resistance in agriculture and biotechnology but also for the optimal use of vaccination against human pathogens.

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Section: Discussionmentioning

confidence: 99%

Building pyramids against the evolutionary emergence of pathogens

Gandon

Guillemet

Gatchitch

et al. 2022

Preprint

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“…In 2021, Chivukula et al, demonstrated the applicability of the mRNA therapeutic platform for multivalent influenza vaccine creation [ 103 ]. Proof-of-concept experiments were successfully completed in mice and nonhuman primates (NHP).…”

Section: Universal Flu Vaccine Perspectivesmentioning

confidence: 99%

“…Each of the aforementioned methods can be delivered via a recently emerged mRNA vehicle platform, e.g., chimeric HA, predicted epitopic peptides, or a cocktail of various IAVs subtypes genome fragments may be inserted into an mRNA cassette. Moreover, multiple mRNA transcripts can be packaged and delivered as a combination with no differences in the impact on the magnitude of humoral immune response, compared with antigen delivered monovalently [ 103 ].…”

Section: Universal Flu Vaccine Perspectivesmentioning

confidence: 99%

Universal Flu mRNA Vaccine: Promises, Prospects, and Problems

et al. 2022

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The seasonal flu vaccine is, essentially, the only known way to prevent influenza epidemics. However, this approach has limited efficacy due to the high diversity of influenza viruses. Several techniques could potentially overcome this obstacle. A recent first-in-human study of a chimeric hemagglutinin-based universal influenza virus vaccine demonstrated promising results. The coronavirus pandemic triggered the development of fundamentally new vaccine platforms that have demonstrated their effectiveness in humans. Currently, there are around a dozen messenger RNA and self-amplifying RNA flu vaccines in clinical or preclinical trials. However, the applicability of novel approaches for a universal influenza vaccine creation remains unclear. The current review aims to cover the current state of this problem and to suggest future directions for RNA-based flu vaccine development.

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“…To limit the number of animals needed, developers can co-encapsulate fluorescent protein-encoding mRNA and luciferase-encoding mRNA in a single LNP, which mimics multivalent mRNA vaccines [158] , [159] . Alternatively, it is also possible to encode an eGFP-Fluc fusion protein on a single mRNA instead [130] .…”

Section: Other Techniques That Could Reach Ema/fda Requirementsmentioning

confidence: 99%