Technological approaches to streamline vaccination schedules, progressing towards single-dose vaccines

Abstract Vaccines represent the most successful medical intervention in history, with billions of lives saved. Although multiple doses of the same vaccine are typically required to reach an adequate level of protection, it would be advantageous to develop vaccines that induce protective immunity with fewer doses, ideally just one. Single-dose vaccines would be ideal to maximize vaccination coverage, help stakeholders to greatly reduce the costs associated with vaccination, and improve patient convenience. Here we describe past attempts to develop potent single dose vaccines and explore the reasons they failed. Then, we review key immunological mechanisms of the vaccine-specific immune responses, and how innovative technologies and approaches are guiding the preclinical and clinical development of potent single-dose vaccines. By modulating the spatio-temporal delivery of the vaccine components, by providing the appropriate stimuli to the innate immunity, and by designing better antigens, the new technologies and approaches leverage our current knowledge of the immune system and may synergize to enable the rational design of next-generation vaccination strategies. This review provides a rational perspective on the possible development of future single-dose vaccines.

Download Full-text

The immune response and the evaluation of acquired immunity against gastrointestinal nematodes in cattle: a review

Parasitology ◽

10.1017/s0031182099005776 ◽

2000 ◽

Vol 120 (7) ◽

pp. 25-42 ◽

Cited By ~ 57

Author(s):

E. CLAEREBOUT ◽

J. VERCRUYSSE

Keyword(s):

Immune Response ◽

Immune Responses ◽

Protective Immunity ◽

Current Knowledge ◽

Small Ruminants ◽

Gastrointestinal Nematodes ◽

Gastrointestinal Parasites ◽

Acquired Immunity ◽

Immunological Parameters ◽

Iga Response

The present review discusses the immune responses to gastrointestinal nematodes in cattle and the different immunological and parasitological parameters used to assess acquired immunity. Measuring acquired immunity to gastrointestinal nematodes in cattle (e.g. for the evaluation of candidate parasite vaccines) is hampered by the limited understanding of bovine immune responses against gastrointestinal parasites. In this paper the available data on protective immunity against gastrointestinal nematodes, and especially Ostertagia ostertagi, in cattle are compared with the current knowledge of protective immune responses against gastrointestinal nematodes in rodent models and small ruminants. In contrast to the immune response in mice, which is controlled by T helper 2 (Th2) lymphocytes and results in mast cell- or goblet cell- mediated expulsion of adult worms, bovine immune responses to O. ostertagi do not show a clear Th2 cytokine profile, nor do they result in rapid expulsion of the parasite. The first manifestation of immunity to O. ostertagi in calves is a reduction of worm fecundity, possibly regulated by the local IgA response. Worm numbers are only reduced after a prolonged period of host–parasite contact, and there are indications that O. ostertagi actively suppresses the host's immune response. Until the mechanisms of protective immunity against O. ostertagi are revealed, the use of immunological parameters to estimate acquired immunity in cattle is based on their correlation with parasitological parameters and on extrapolation from rodent and small ruminant models. Assessing the resistance of calves against a challenge infection by means of parasitological parameters is probably still the most accurate way to measure acquired immunity against gastrointestinal nematodes.

Download Full-text

Protective Immunity against Vibrio harveyi in Grouper Induced by Single Vaccination with Poly (Lactide-co-glycolide) Microparticles Releasing Pleurocidin Peptide and Recombinant Glyceraldehyde-3-phosphate Dehydrogenase

Vaccines ◽

10.3390/vaccines8010033 ◽

2020 ◽

Vol 8 (1) ◽

pp. 33

Author(s):

Shang-Pin Liu ◽

Shu-Chun Chuang ◽

Chung-Da Yang

Keyword(s):

Single Dose ◽

Immune Responses ◽

Protective Immunity ◽

Vibrio Harveyi ◽

Attractive Feature ◽

Tnf Α ◽

Single Vaccination ◽

Highly Virulent ◽

Dose Vaccine

The peptide adjuvant, pleurocidin (PLE), and the Vibrio harveyi antigen, recombinant glyceraldehyde-3-phosphate dehydrogenase (rGAPDH) protein, were encapsulated with poly (lactide-co-glycolide) (PLG) polymers in our previous study to produce PLG-encapsulated PLE plus rGAPDH microparticles (PLG-PLE/rGAPDH MPs) that sustained stable release of both PLE and rGAPDH as well as, after two-time vaccination with MPs, generated long-term protective immunity against V. harveyi in grouper. Stable controlled-release of PLE plus rGAPDH from PLG-PLE/rGAPDH MPs is an attractive feature for developing an effective single-dose vaccine. In the present study, therefore, we aim to evaluate whether single administration with PLG-PLE/rGAPDH MPs in grouper would result in protective immunity against V. harveyi. Peritoneal vaccination of grouper with one dose of PLG-PLE/rGAPDH MPs raised serum titers over a long 12-week period. Moreover, twelve weeks after vaccination, significant lymphocyte proliferation and maximum TNF-α production were found in grouper immunized with a single dose of PLG-PLE/rGAPDH MPs. More importantly, immune responses elicited by single vaccination with PLG-PLE/rGAPDH MPs protected 80% of fish against a lethal peritoneal challenge of the highly virulent V. harveyi (Vh MML-1). In conclusion, our data truly reveal the feasibility of the development of a single-dose vaccine against V. harveyi based on PLG-PLE/rGAPDH MPs.

Download Full-text

Understanding Host Immunity and the Gut Microbiota Inspires the New Development of Vaccines and Adjuvants

Pharmaceutics ◽

10.3390/pharmaceutics13020163 ◽

2021 ◽

Vol 13 (2) ◽

pp. 163

Author(s):

Kyosuke Yakabe ◽

Jun Uchiyama ◽

Masahiro Akiyama ◽

Yun-Gi Kim

Keyword(s):

Gut Microbiota ◽

Immune Responses ◽

Immune Cells ◽

Current Knowledge ◽

Innate Immune ◽

Innate Immune Cells ◽

Mortality And Morbidity ◽

Complex Interactions ◽

Immunological Mechanisms ◽

New Development

Vaccinations improve the mortality and morbidity rates associated with several infections through the generation of antigen-specific immune responses. Adjuvants are often used together with vaccines to improve immunogenicity. However, the immune responses induced by most on-going vaccines and adjuvants approved for human use vary in individuals; this is a limitation that must be overcome to improve vaccine efficacy. Several reports have indicated that the symbiotic bacteria, particularly the gut microbiota, impact vaccine-mediated antigen-specific immune responses and promote the induction of nonspecific responses via the “training” of innate immune cells. Therefore, the interaction between gut microbiota and innate immune cells should be considered to ensure the optimal immunogenicity of vaccines and adjuvants. In this review, we first introduce the current knowledge on the immunological mechanisms of vaccines and adjuvants. Subsequently, we discuss how the gut microbiota influences immunity and highlight the relationship between gut microbes and trained innate immunity, vaccines, and adjuvants. Understanding these complex interactions will provide insights into novel vaccine approaches centered on the gut microbiota.

Download Full-text

Rational Vaccine Design in Times of Emerging Diseases: The Critical Choices of Immunological Correlates of Protection, Vaccine Antigen and Immunomodulation

Pharmaceutics ◽

10.3390/pharmaceutics13040501 ◽

2021 ◽

Vol 13 (4) ◽

pp. 501

Author(s):

Virgil Schijns ◽

Dragomira Majhen ◽

Peter van der Ley ◽

Aneesh Thakur ◽

Artur Summerfield ◽

...

Keyword(s):

Rational Design ◽

Current Knowledge ◽

Medical Intervention ◽

Emerging Diseases ◽

Vaccine Antigen ◽

Vaccine Adjuvant ◽

Correlates Of Protection ◽

Immune Correlates ◽

Life Threatening ◽

Rational Vaccine Design

Vaccines are the most effective medical intervention due to their continual success in preventing infections and improving mortality worldwide. Early vaccines were developed empirically however, rational design of vaccines can allow us to optimise their efficacy, by tailoring the immune response. Establishing the immune correlates of protection greatly informs the rational design of vaccines. This facilitates the selection of the best vaccine antigens and the most appropriate vaccine adjuvant to generate optimal memory immune T cell and B cell responses. This review outlines the range of vaccine types that are currently authorised and those under development. We outline the optimal immunological correlates of protection that can be targeted. Finally we review approaches to rational antigen selection and rational vaccine adjuvant design. Harnessing current knowledge on protective immune responses in combination with critical vaccine components is imperative to the prevention of future life-threatening diseases.

Download Full-text

Humanized Mice for Live-Attenuated Vaccine Research: From Unmet Potential to New Promises

Vaccines ◽

10.3390/vaccines8010036 ◽

2020 ◽

Vol 8 (1) ◽

pp. 36 ◽

Cited By ~ 1

Author(s):

Aoife K. O’Connell ◽

Florian Douam

Keyword(s):

Immune System ◽

Immune Responses ◽

Rational Design ◽

Cost Effective ◽

Yellow Fever Vaccine ◽

Human Immune System ◽

Live Attenuated Vaccine ◽

The Past ◽

Immunological Mechanisms ◽

Human Immune

Live-attenuated vaccines (LAV) represent one of the most important medical innovations in human history. In the past three centuries, LAV have saved hundreds of millions of lives, and will continue to do so for many decades to come. Interestingly, the most successful LAVs, such as the smallpox vaccine, the measles vaccine, and the yellow fever vaccine, have been isolated and/or developed in a purely empirical manner without any understanding of the immunological mechanisms they trigger. Today, the mechanisms governing potent LAV immunogenicity and long-term induced protective immunity continue to be elusive, and therefore hamper the rational design of innovative vaccine strategies. A serious roadblock to understanding LAV-induced immunity has been the lack of suitable and cost-effective animal models that can accurately mimic human immune responses. In the last two decades, human-immune system mice (HIS mice), i.e., mice engrafted with components of the human immune system, have been instrumental in investigating the life-cycle and immune responses to multiple human-tropic pathogens. However, their use in LAV research has remained limited. Here, we discuss the strong potential of LAVs as tools to enhance our understanding of human immunity and review the past, current and future contributions of HIS mice to this endeavor.

Download Full-text

Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

International Journal of Molecular Sciences ◽

10.3390/ijms22031201 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1201

Author(s):

Hsuan Peng ◽

Kazuhiro Shindo ◽

Renée R. Donahue ◽

Ahmed Abdel-Latif

Keyword(s):

Stem Cell ◽

Immune Responses ◽

Tissue Repair ◽

Molecular Mechanisms ◽

Clinical Evidence ◽

Current Knowledge ◽

Cell Delivery ◽

Cardiac Cell Therapy ◽

Stem Cell Treatment

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.

Download Full-text

Beta-Blockade in Intraseptal Anomalous Coronary Artery With Reversible Myocardial Ischemia

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/2150135120954818 ◽

2021 ◽

Vol 12 (1) ◽

pp. 145-148

Author(s):

Tam T. Doan ◽

Athar M. Qureshi ◽

Shagun Sachdeva ◽

Cory V. Noel ◽

Dana Reaves-O’Neal ◽

...

Keyword(s):

Coronary Artery ◽

Myocardial Ischemia ◽

Dobutamine Stress ◽

Medical Intervention ◽

Beta Blockade ◽

Fractional Flow ◽

Flow Reserve ◽

Reversible Ischemia ◽

Improve Patient

Anomalous aortic origin of a left coronary artery (L-AAOCA) with an intraseptal course is a rare anomaly and can be associated with myocardial ischemia and sudden cardiac death. No surgical or medical intervention is known to improve patient outcomes. A 7-year-old boy with intraseptal L-AAOCA presented with nonexertional chest pain, syncope, and had reversible myocardial ischemia on provocative testing. The patient was started on β-blockade, following which his symptoms improved and resolved over a period of six years. A follow-up dobutamine stress magnetic resonance imaging no longer showed reversible ischemia, and cardiac catheterization with fractional flow reserve did not show coronary flow compromise.

Download Full-text

Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants

Vaccines ◽

10.3390/vaccines9020095 ◽

2021 ◽

Vol 9 (2) ◽

pp. 95

Author(s):

Daisuke Tokuhara ◽

Norikatsu Hikita

Keyword(s):

Cord Blood ◽

Protective Immunity ◽

Current Knowledge ◽

Current System ◽

Innate Immune ◽

Vaccine Adjuvants ◽

Adult Humans ◽

Neonates And Infants ◽

Induced Immunity ◽

Review Current

Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood.

Download Full-text

Phony peach disease: past and present impact on the peach industry in the southeastern U.S.A

CABI Agriculture and Bioscience ◽

10.1186/s43170-021-00049-4 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Kendall A. Johnson ◽

Clive H. Bock ◽

Phillip M. Brannen

Keyword(s):

New Technologies ◽

Current Knowledge ◽

Future Research ◽

Management Options ◽

Disease Epidemiology ◽

Pathogen Diversity ◽

Foundational Research ◽

Global Threat ◽

And Control ◽

The Impact

Abstract Background Phony peach disease (PPD) is caused by the plant pathogenic bacterium Xylella fastidiosa subsp. multiplex (Xfm). Historically, the disease has caused severe yield loss in Georgia and elsewhere in the southeastern United States, with millions of PPD trees being removed from peach orchards over the last century. The disease remains a production constraint, and management options are few. Limited research has been conducted on PPD since the 1980s, but the advent of new technologies offers the opportunity for new, foundational research to form a basis for informed management of PPD in the U.S. Furthermore, considering the global threat of Xylella to many plant species, preventing import of Xfm to other regions, particularly where peach is grown, should be considered an important phytosanitary endeavor. Main topics We review PPD, its history and impact on peach production, and the eradication efforts that were conducted for 42 years. Additionally, we review the current knowledge of the pathogen, Xfm, and how that knowledge relates to our understanding of the peach—Xylella pathosystem, including the epidemiology of the disease and consideration of the vectors. Methods used to detect the pathogen in peach are discussed, and ramifications of detection in relation to management and control of PPD are considered. Control options for PPD are limited. Our current knowledge of the pathogen diversity and disease epidemiology are described, and based on this, some potential areas for future research are also considered. Conclusion There is a lack of recent foundational research on PPD and the associated strain of Xfm. More research is needed to reduce the impact of this pathogen on peach production in the southeastern U.S., and, should it spread internationally, wherever peaches are grown.

Download Full-text

Review of Current Spinal Robotic Orthoses

Healthcare ◽

10.3390/healthcare9010070 ◽

2021 ◽

Vol 9 (1) ◽

pp. 70

Author(s):

Siu Kei David Mak ◽

Dino Accoto

Keyword(s):

New Technologies ◽

Current Knowledge ◽

Axial Loading ◽

Early Mobilization ◽

Bed Rest ◽

Field Application ◽

Symptomatic Management ◽

Spinal Brace ◽

Potential Improvement ◽

Spinal Orthosis

Osteoporotic spine fractures (OSF) are common sequelae of osteoporosis. OSF are directly correlated with increasing age and incidence of osteoporosis. OSF are treated conservatively or surgically. Associated acute pain, chronic disabilities, and progressive deformities are well documented. Conservative measures include a combination of initial bed rest, analgesia, early physiotherapy, and a spinal brace (orthosis), with the aim for early rehabilitation to prevent complications of immobile state. Spinal bracing is commonly used for symptomatic management of OSF. While traditional spinal braces aim to maintain the neutral spinal alignment and reduce the axial loading on the fractured vertebrae, they are well known for complications including discomfort with reduced compliance, atrophy of paraspinal muscles, and restriction of chest expansion leading to chest infections. Exoskeletons have been developed to passively assist and actively augment human movements with different types of actuators. Flexible, versatile spinal exoskeletons are designed to better support the spine. As new technologies enable the development of motorized wearable exoskeletons, several types have been introduced into the medical field application. We have provided a thorough review of the current spinal robotic technologies in this paper. The shortcomings in the current spinal exoskeletons were identified. Their limitations on the use for patients with OSF with potential improvement strategies were discussed. With our current knowledge of spinal orthosis for conservatively managed OSF, a semi-rigid backpack style thoracolumbar spinal robotic orthosis will reduce spinal bone stress and improve back muscle support. This will lead to back pain reduction, improved posture, and overall mobility. Early mobilization is an important part of management of patients with OSF as it reduces the chance of developing complications related to their immobile state for patients with OSF, which will be helpful for their recovery.

Download Full-text