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Review
. 2020 Sep 18:5:88.
doi: 10.1038/s41541-020-00238-8. eCollection 2020.

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

Giuseppe Lofano  1 , Corey P Mallett  1 , Sylvie Bertholet  1 , Derek T O'Hagan  1
Affiliations
Review

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

Giuseppe Lofano et al. NPJ 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.

Keywords: Business strategy in drug development; DNA vaccines; Drug delivery; Drug development; Vaccines.

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Conflict of interest statement

Competing interestsG.L., C.P.M., S.B., and D.T.H. are employees of the GSK group of companies.

Figures

Fig. 1
Fig. 1. The journey of the vaccine components after injection.
Intramuscular or subcutaneous injection triggers the recruitment of immune cells to the site of injection, where they activate, capture the antigen and migrate to the draining lymph node. Antigens, adjuvants or other components smaller than 10–100 nm may also diffuse in the lymphatic systems and reach the lymph node through the afferent lymphatics. While smaller molecules (<70 kDa) may diffuse through fenestrae of the subcapsular sinus, the largest molecules are transferred to the B cells with the help of subcapsular sinus macrophages. B cells and resident dendritic cells may also sense molecules in the conduits and transfer them to the B cell area to initiate the germinal center responses.
Fig. 2
Fig. 2. Approaches for the rational design of potent single-dose vaccines.
A rational design of potent single-dose vaccines can be achieved by modulating the spatial and temporal deliveries of the vaccine components, by designing multivalent antigens and by efficiently engaging the innate immunity. The muscle and the draining lymph node are the two most important sites for targeted delivery of antigen and immune stimuli, which can be achieved by modulating the biophysical and biochemical properties of the vaccine components. Antigen persistence in germinal center regions of lymph nodes is essential to promote robust immune responses and can be modulated with controlled-release materials, DNA, RNA, viral vectors, or adjuvants. Antigens can be designed as virus-like particles (VLPs) to present a multivalent conformation and promote efficient B cell receptor engagement on the surface of B cells. Furthermore, activation of innate immune cells is essential to induce strong antigen-specific immune responses and can be achieved by engaging pattern recognition receptors with adjuvants, nucleic acids, and viral vectors vaccines.
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References

    1. Azman AS, et al. Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study. Lancet Glob. Health. 2016;4:e856–e863. - PubMed
    1. Peck, M. et al. CDC. Global Routine Vaccination Coverage (2018). - PMC - PubMed
    1. Kurosky SK, Davis KL, Krishnarajah G. Completion and compliance of childhood vaccinations in the United States. Vaccine. 2016;34:387–394. - PubMed
    1. Ventola, C. L. Immunization in the United States: recommendations, barriers, and measures to improve compliance. P&T (2016). - PMC - PubMed
    1. Cohen, J. How long do vaccines last? The surprising answers may help protect people longer. https://www.sciencemag.org (2019).