Formulation and Delivery Technologies for mRNA Vaccines

Zeng, Chunxi; Zhang, Chengxiang; Walker, Patrick; Dong, Yizhou

doi:10.1007/82_2020_217

Cited by 134 publications

(149 citation statements)

References 244 publications

(357 reference statements)

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“…[ 20 ] Delivery of nucleic acid vaccines can be improved by incorporation into particle delivery systems to facilitate cellular entry and protect the cargo from nuclease degradation. [ 21 ] Polymeric encapsulation or complexation has been used to deliver mRNA and other nucleic acid vaccines, [ 22 ] but complexing it to cationic and ionizable lipids is much more common. Indeed, the two leading vaccine candidates for the COVID‐19 pandemic, developed by Moderna and Pfizer/BioNTech, are a lipid nanoparticle (NP) that complexes mRNA encoding the SARS‐CoV‐2 spike protein.…”

Section: Introductionmentioning

confidence: 99%

Considerations for Size, Surface Charge, Polymer Degradation, Co‐Delivery, and Manufacturability in the Development of Polymeric Particle Vaccines for Infectious Diseases

Genito

Batty

Bachelder

et al. 2021

Advanced NanoBiomed Research

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Vaccines have advanced human health for centuries. To improve upon the efficacy of subunit vaccines they have been formulated into nano/microparticles for infectious diseases. Much progress in the field of polymeric particles for vaccine formulation has been made since the push for a tetanus vaccine in the 1990s. Modulation of particle properties such as size, surface charge, degradation rate, and the co‐delivery of antigen and adjuvant has been used. This review focuses on advances in the understanding of how these properties influence immune responses to injectable polymeric particle vaccines. Consideration is also given to how endotoxin, route of administration, and other factors influence conclusions that can be made. Current manufacturing techniques involved in preserving vaccine efficacy and scale‐up are discussed, as well as those for progressing polymeric particle vaccines toward commercialization. Consideration of all these factors should aid the continued development of efficacious and marketable polymeric particle vaccines.

show abstract

Section: Introductionmentioning

confidence: 99%

Considerations for Size, Surface Charge, Polymer Degradation, Co‐Delivery, and Manufacturability in the Development of Polymeric Particle Vaccines for Infectious Diseases

Genito

Batty

Bachelder

et al. 2021

Advanced NanoBiomed Research

View full text Add to dashboard Cite

show abstract

“…RNA vaccines are designed using the genetic sequence of the viral antigen and rapidly manufactured using cell-free, rapidly scalable techniques [14]. The RNA is encapsulated in a lipid nanoparticle (LNP), which generates robust immune responses without the need for adjuvants [15,16].…”

Section: Introductionmentioning

confidence: 99%

A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice

Alwis

Gan

Chen

et al. 2020

Preprint

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A self-transcribing and replicating RNA (STARR™) based vaccine (LUNAR®-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolong SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell mediated immunity produced a strong viral antigen specific CD8+ T lymphocyte response. Assaying for intracellular cytokine staining for IFN-γ and IL-4 positive CD4+ T helper lymphocytes as well as anti-spike glycoprotein IgG2a/IgG1 ratios supported a strong Th1 dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 μg and 10 μg doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of Lunar-COV19 as a single dose vaccine.

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“…However, due to their nature of easily disintegrating and a lack of efficient internalization by host cells, mRNA vaccines demand highly reliable and efficient delivery systems. Encapsulation of the vaccine by delivery systems or carriers comprises various types like peptides, polymers, nanoparticles (especially lipids), naked mRNA in solution and ex vivo via APCs like dendritic cells [17].…”

Section: Mechanism Of Action Of Mrna Vaccines In Fighting Covid-19mentioning

confidence: 99%

Can mRNA Vaccines Turn the Tables During the COVID-19 Pandemic? Current Status and Challenges

et al. 2021

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The COVID-19 pandemic continues to affect millions of people across the world. The current global statistics for the disease are 111 million cases and 2.45 million deaths, with new cases emerging each day. Although several drugs including remdesivir have been approved for emergency use, they remain ineffective in bringing the infection under control. Therefore, there is a need for highly effective and safe vaccines against COVID-19. The recent advancements in mRNA vaccines have catapulted them to be forefront in the race to develop vaccines for COVID-19. Two mRNA vaccines, BNT162b2 and mRNA-1273, developed by Pfizer-BioNTech and Moderna Therapeutics, respectively, have been granted authorization for emergency use by the US Food and Drug Administration. Interim analysis of the clinical trials for BNT162b2 and mRNA-1273 vaccines reported an efficacy of 95% and 94.1%, respectively, after the second dose. The adverse events for both the vaccines have been found to be mild to moderate, with mostly injection-site reactions and fatigue. No serious adverse events have been reported. Moreover, Pfizer-BioNTech and Moderna Therapeutics have announced that their vaccines are effective even against the new strains (B.1.17 and B.1.351) of the virus. Both companies are now scaling up the production of the vaccines to meet the global demand. Although the long-term efficacy, safety, and immunogenicity of these vaccines is uncertain, there is hope that they can turn the tables against COVID-19 in this current pandemic situation.

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Formulation and Delivery Technologies for mRNA Vaccines

Cited by 134 publications

References 244 publications

Considerations for Size, Surface Charge, Polymer Degradation, Co‐Delivery, and Manufacturability in the Development of Polymeric Particle Vaccines for Infectious Diseases

Considerations for Size, Surface Charge, Polymer Degradation, Co‐Delivery, and Manufacturability in the Development of Polymeric Particle Vaccines for Infectious Diseases

A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice

Can mRNA Vaccines Turn the Tables During the COVID-19 Pandemic? Current Status and Challenges

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