Recent advances in micro- and nano-scale carrier systems for controlled delivery of vaccines
Vaccines provide substantial safety against infectious diseases, saving millions of lives each year. The recent COVID-19 pandemic highlighted the importance of vaccination in providing mass-scale immunization against outbreaks. However, the delivery of vaccines imposes a unique set of challenges due to their large molecular size and low room temperature stability. Advanced biomaterials and delivery systems such as micro- and nanoscale carriers are becoming critical components for successful vaccine developments.
In this review, we provide an updated overview of recent advances in the development of micro- and nano-scale carriers for controlled delivery of vaccines, focusing on carriers compatible with nucleic acid-based vaccines and therapeutics that emerged amid the recent pandemic. We start by detailing nanoscale delivery systems, focusing on nanoparticles, then move on to microscale systems including hydrogels, microparticles, and 3D printed microneedle patches. Additionally, we delve into emerging methods that move beyond traditional needle-based applications utilizing innovative delivery systems. Future challenges in clinical translation and manufacturing in this rapidly advancing field are also discussed.
Introduction
Vaccines are estimated to rescue approximately 8 million lives annually [[1], [2], [3]]. The implementation of the World Health Organization’s (WHO) Expanded Program on Immunization (EPI) has substantially increased vaccination rates from 5 % in 1974 to nearly 84 % [4,5]. However, approximately one in six infants remains inadequately immunized annually, leading to the deaths of approximately 1.5 million children under the age of 5 due to vaccine-preventable diseases every year [4,5]. Logistic barriers, such as the need for storage at low temperatures (i. e. −80 °C) or the need for multiple doses, weeks or months apart, remain a key contributor to underimmunization [6,7]. For example, almost half of under-immunized infants have received at least one dose of vaccines against diphtheria, tetanus, and pertussis but remain susceptible to these diseases due to the incomplete three-dose series [4]. While a single bolus vaccine dose can achieve seroprotection rates in the range of 75 %–90 % [8,9], full immunization entails scheduling multiple doses to ensure immunity levels reach nearly 100 % [8,10]. Increasing convenience, vaccine stability, reducing dosing regimen, and enhancing dosing efficiency can potentially help eliminate these issues. Developing vaccine carriers with controlled release kinetics which can reduce the frequency of injections and mimic current vaccines regimens while maintaining vaccine stability at the physical temperature would be an essential step towards this goal.
In a simplified form, vaccines function by prompting the adaptive immune system’s immunological memory to identify and combat specific pathogens. Traditionally, vaccines contain weakened or inactive components of the disease-causing antigen [11,12]. Upon vaccination, an individual’s immune system generates antibodies against the antigen included in the vaccine. These antibodies collaborate with the rest of the immune system to eliminate an attenuated version of the pathogenic insult [11,12]. In the event of future exposures to the same pathogen, the immune system will be trained to respond swiftly, providing long-term protection [11,12]. A comprehensive overview of the mechanism behind vaccine-mediated immunity against infectious diseases has been covered in several review papers [12,15,16]. More recent vaccines are based on nucleic acid payloads (e. g. mRNA, DNA) [[13], [14], [15], [16]]. In this approach, instead of delivering an inactivated antigen, a sequence of nucleic acids incorporating the genetic information is delivered to cells to encode the full structure or pathogenic subdomains on the antigen of interest. Nucleic acid-based vaccines outpaced conventional methods during the recent pandemic response due to their swift production, eliminating the extended cultivation and purification steps associated with egg- or cell-based vaccine manufacturing. Their synthesis is highly scalable, the purification process is straightforward, and the technology platforms are easily adaptable, allowing for rapid response and development when facing emerging infectious threats.
Developing effective vaccine delivery systems with desired kinetics has long been a critical issue [17]. The recent covid pandemic has further drawn global attention to vaccine delivery systems. Even prior, effective administration of vaccines globally was considered a powerful tool against widespread infectious diseases. Significant advances in biomedical technology and more specifically drug delivery systems have substantially propelled the field of vaccine delivery by introducing novel technologies in micro and nanoscales. This has further been accelerated by introduction of structurally complex vaccines such as mRNA vaccines encapsulated in lipid nanoparticles (LNPs) which currently require extremely low temperatures for storage [18,19]. These factors collectively motivate establishing a comprehensive review of the most recent advances in vaccine delivery as a guide for future research. In this review, we focus on preclinical cutting-edge research in micro and nanoscales for controlled delivery of vaccines. We aim to provide an overview of technologies used not only for traditional vaccines such as protein and peptide-based vaccines but also for recently developed nucleic acid-based vaccines, including DNA and mRNA. We first overview nanoscale vaccine delivery technologies developed to date, then describe microscale-based technologies. Exploring beyond traditional delivery modalities, we also describe alternative, needle-free methodologies utilizing these carriers. Finally, we discuss key challenges for manufacturing and clinical translation of vaccine delivery systems. This review emphasizes delivery systems and platform technologies uniquely crafted for prophylactic vaccine administration. While we touch upon systems developed for other therapeutic applications, such as cancer vaccines, we highlight their potential relevance to vaccine delivery for infectious diseases. It’s noteworthy that comprehensive discussions on general mRNA therapeutics are described in depth elsewhere [20,21].
Read more
Erika Yan Wang, Morteza Sarmadi, Binbin Ying, Ana Jaklenec, Robert Langer, Recent advances in micro- and nano-scale carrier systems for controlled delivery of vaccines, Biomaterials, 2023, 122345, ISSN 0142-9612,
https://doi.org/10.1016/j.biomaterials.2023.122345.
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