Engineered Migrasomes: A Robust, Thermally Stable Vaccination Platform
Curation statements for this article:-
Curated by eLife
eLife assessment
The study, from the group that pioneered migrasome, describes a novel vaccine platform derived from this newly discovered organelle. Using these cleverly engineered migrasomes – that behave like natural migrasomes – as a novel vaccine platform has the potential to overcome obstacles such as cold chain issues for vaccines like messenger RNA. Although the findings are important with practical implications for the vaccine technology, and the evidence, based on appropriate and validated methodology is convincing and is in line with current state-of-the-art, there are some critical issues that need to be addressed. These include a head-to-head comparison with proven vaccine platforms, for example, a SARS-CoV-2 mRNA vaccine or an adjuvanted recombinant spike protein.
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (eLife)
Abstract
The burgeoning abilities of pathogens and tumor cells to evade immune responses underscore the urgent need for innovative vaccination platforms based on a variety of biological mechanisms. The current logistical challenges associated with cold-chain (i.e. low-temperature) transportation particularly impacts access to vaccines in the global south. We recently discovered organelles called migrasomes, and herein we investigate the potential of migrasomes as an alternative vaccination platform. Their inherent stability and their enrichment with immune-modulating molecules make migrasomes promising candidates, but their low yield presents a hurdle. We address this problem through our engineered migrasome-like vesicles (eMigrasomes), which emulate the biophysical attributes of natural migrasomes with substantially improved yield. We show that eMigrasomes loaded with a model antigen elicit potent antibody responses and maintain stability at room temperature. We demonstrate that eMigrasomes bearing the SARS-CoV-2 Spike protein induce robust humoral protection against the virus. Our study demonstrates the potential of eMigrasome-based vaccines as a unique, robust, and accessible alternative to traditional methods.
Article activity feed
-
-
-
eLife assessment
The study, from the group that pioneered migrasome, describes a novel vaccine platform derived from this newly discovered organelle. Using these cleverly engineered migrasomes – that behave like natural migrasomes – as a novel vaccine platform has the potential to overcome obstacles such as cold chain issues for vaccines like messenger RNA. Although the findings are important with practical implications for the vaccine technology, and the evidence, based on appropriate and validated methodology is convincing and is in line with current state-of-the-art, there are some critical issues that need to be addressed. These include a head-to-head comparison with proven vaccine platforms, for example, a SARS-CoV-2 mRNA vaccine or an adjuvanted recombinant spike protein.
-
Reviewer #1 (Public Review):
Summary:
This is an excellent study by a superb investigator who discovered and is championing the field of migrasomes. This study contains a hidden "gem" - the induction of migrasomes by hypotonicity and how that happens. In summary, an outstanding fundamental phenomenon (migrasomes) en route to becoming transitionally highly significant.Strengths:
Innovative approach at several levels. Migrasomes - discovered by Dr Yu's group - are an outstanding biological phenomenon of fundamental interest and now of potentially practical value.
Weaknesses:
I feel that the overemphasis on practical aspects (vaccine), however important, eclipses some of the fundamental aspects that may be just as important and actually more interesting. If this can be expanded, the study would be outstanding.
-
Reviewer #2 (Public Review):
Summary:
The authors' report describes a novel vaccine platform derived from a newly discovered organelle called a migrasome. First, the authors address a technical hurdle in using migrasomes as a vaccine platform. Natural migrasome formation occurs at low levels and is labor intensive, however, by understanding the molecular underpinning of migrasome formation, the authors have designed a method to make engineered migrasomes from cultured, cells at higher yields utilizing a robust process. These engineered migrasomes behave like natural migrasomes. Next, the authors immunized mice with migrasomes that either expressed a model peptide or the SARS-CoV-2 spike protein. Antibodies against the spike protein were raised that could be boosted by a 2nd vaccination and these antibodies were functional as assessed by …
Reviewer #2 (Public Review):
Summary:
The authors' report describes a novel vaccine platform derived from a newly discovered organelle called a migrasome. First, the authors address a technical hurdle in using migrasomes as a vaccine platform. Natural migrasome formation occurs at low levels and is labor intensive, however, by understanding the molecular underpinning of migrasome formation, the authors have designed a method to make engineered migrasomes from cultured, cells at higher yields utilizing a robust process. These engineered migrasomes behave like natural migrasomes. Next, the authors immunized mice with migrasomes that either expressed a model peptide or the SARS-CoV-2 spike protein. Antibodies against the spike protein were raised that could be boosted by a 2nd vaccination and these antibodies were functional as assessed by an in vitro pseudoviral assay. This new vaccine platform has the potential to overcome obstacles such as cold chain issues for vaccines like messenger RNA that require very stringent storage conditions.
Strengths:
The authors present very robust studies detailing the biology behind migrasome formation and this fundamental understanding was used to form engineered migrasomes, which makes it possible to utilize migrasomes as a vaccine platform. The characterization of engineered migrasomes is thorough and establishes comparability with naturally occurring migrasomes. The biophysical characterization of the migrasomes is well done including thermal stability and characterization of the particle size (important characterizations for a good vaccine).
Weaknesses:
With a new vaccine platform technology, it would be nice to compare them head-to-head against a proven technology. The authors would improve the manuscript if they made some comparisons to other vaccine platforms such as a SARS-CoV-2 mRNA vaccine or even an adjuvanted recombinant spike protein. This would demonstrate a migrasome-based vaccine could elicit responses comparable to a proven vaccine technology. Additionally, understanding the integrity of the antigens expressed in their migrasomes could be useful. This could be done by looking at functional monoclonal antibodies binding to their migrasomes in a confocal microscopy experiment.
-
