Lipid nanoparticles in the development of mRNA vaccines for COVID-19

Wilson, Barnabas; Geetha, K

doi:10.1016/j.jddst.2022.103553

Cited by 100 publications

(58 citation statements)

References 65 publications

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“…LNP are novel adjuvant components that can be incorporated into mRNA vaccines. LNP-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against SARS-CoV-2 ( 26 ), and animal experiments have demonstrated that LNP has intrinsic adjuvant activity ( 27 ). The dose of eLNP was set as lipid content equivalent to 5 µg mRNA-LNP, the dose at which mRNA-LNP induces an acquired immune response ( Supplementary Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component

Yoshioka

Kobiyama²,

Hayashi³

et al. 2023

Front. Immunol.

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BackgroundAdjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.Methods and ResultsTo characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.ConclusionsThis study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants.

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Section: Resultsmentioning

confidence: 99%

A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component

Yoshioka

Kobiyama²,

Hayashi³

et al. 2023

Front. Immunol.

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“…In preclinical studies, CureVac has demonstrated that the sequence-optimized rabies virus vaccine in development, RABV-G, could remain stable for several months in the region between -80°C and 70°C ( 73 ). Furthermore, two investigational mRNA COVID-19 vaccines had now been reported to be able to remain stable in a room temperature environment ( 74 , 75 ). If these heat-resistant vaccine candidates achieve positive results in clinical trials, it is expected to improve the global accessibility of mRNA vaccines ( Table 3 ).…”

Section: Mrna Drug Key Development Technologies and Challengesmentioning

confidence: 99%

How far are the new wave of mRNA drugs from us? mRNA product current perspective and future development

Duan

Zhu

et al. 2022

Front. Immunol.

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mRNA products are therapies that are regulated from the post-transcriptional, pre-translational stage of a gene and act upstream of protein synthesis. Compared with traditional small molecule drugs and antibody drugs, mRNA drugs had the advantages of simple design, short development cycle, strong target specificity, wide therapeutic field, and long-lasting effect. mRNA drugs were now widely used in the treatment of genetic diseases, tumors, and viral infections, and are expected to become the third major class of drugs after small molecule drugs and antibody drugs. The delivery system technology was the key to ensuring the efficacy and safety of mRNA drugs, which plays an important role in protecting RNA structure, enhancing targeting ability, reducing the dose of drug delivery, and reducing toxic side effects. Lipid nanoparticles (LNP) were the most common delivery system for mRNA drugs. In recent years, mRNA drugs have seen rapid development, with the number of drugs on the market increasing each year. The success of commercializing mRNA vaccines has driven a wave of nucleic acid drug development. mRNA drugs were clinically used in genetic diseases, oncology, and infectious diseases worldwide, while domestic mRNA clinical development was focused on COVID-19 vaccines, with more scope for future indication expansion.

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“…Anaphylaxis was found in a small sample of the population receiving the BNT162b2 vaccine [13]. Based on the findings, the USFDA approved BNT162b2 as the first COVID-19 vaccination for emergency use [14].…”

Section: Bnt162b2 Mrna Vaccinementioning

confidence: 99%

COVID-19 Vaccine Clinical Trials: A Bird’s Eye Perspective

Chennakesavulu¹,

Cuddapah²,

Keesara³

et al. 2022

Cureus

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Several Phase-III clinical studies investigating vaccine safety and effectiveness have been published a year following the first breakout of the COVID-19 pandemic. These vaccine candidates were produced using a variety of vaccination technologies, including mRNA, recombinant protein, adenoviral vector, and inactivated virus-based platforms, by various research organizations and pharmaceutical firms. Despite many successful clinical studies, participants are restricted by trial inclusion and exclusion criteria, geographic location, and the current state of the virus epidemic. Many concerns remain, particularly for specific populations such as the elderly, women who are pregnant or nursing, and teenagers. Vaccine effectiveness against asymptomatic infection and particular viral variations, on the other hand, is still largely unclear. This review will focus on vaccination candidates that have completed Phase-III clinical trials and will examine the scientific evidence that has been gathered so far for these vaccine candidates for various subgroups of individuals and virus variations.

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Lipid nanoparticles in the development of mRNA vaccines for COVID-19

Cited by 100 publications

References 65 publications

A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component

A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component

How far are the new wave of mRNA drugs from us? mRNA product current perspective and future development

COVID-19 Vaccine Clinical Trials: A Bird’s Eye Perspective

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