The Yin–Yang arms of vaccines: disease-fighting power versus tissue-destructive inflammation

Abstract

The disease-fighting power of vaccines has defeated many pathogens and has been credited with global reduction of mortality and morbidity. However, most vaccine developments focus on the enhancement of effector responses with systemic inflammation and the consequences overlooked. Recent evidence shows that systemic inflammatory phenotypes, acute or chronic, are both detrimental and should be avoided if possible. Since noninvasive vaccination by painless delivery of nasal vaccines and skin patch vaccines could elicit potent protective immunity without inducing systemic inflammation, it can be predicted that vaccinology will increasingly see the abandonment of the ‘needle-injection’ paradigm for vaccine development. The findings that specific viral particles could rapidly remodel the tissue environment postinfection in favor of some pathogens with the capacity to suppress others illustrate the pressing need for a deeper understanding of the underlying mechanisms in order to unlock the full potential of immunological intervention.

Keywords::

• inflammation
• injectable vaccine
• innate immunity
• nasal vaccine
• regulatory T cell
• skin patch vaccine
• vaccine
• vaccine safety

Acknowledgements

The authors thank University of Alabama at Birmingham for providing the animal facility during the development of the innate-adaptive immunity duo platform technology and noninvasive vaccines, as well as performing a human clinical trial of an adenovirus-vectored nasal avian influenza (H5N1) vaccine; E Bart Tarbet at Utah State University for validating the drug-vaccine duo (DVD) data through NIAID Non-Clinical Evaluation Agreements; Southern Drug Research for performing a human clinical trial of adenovirus-vectored nasal and skin patch influenza (H1N1) vaccines.

Financial & competing interests disclosure

DC Tang is the Founder and a shareholder of Vaxin Inc. and an inventor on patents pertaining to skin patch vaccines, adenovirus-vectored vaccines, and drug-vaccine duo (DVD). DC Tang was supported in part by the Korean Brain Pool Program, Chung-Ang University (Seoul, Korea), Biomedical Advanced Research and Development Authority (BARDA) contract HHSO100201100032C, National Institutes of Health (NIH) Small Business Innovation Research Program Phase II grant 2-R44-AI-068285-02, and NIH Challenge grant 1-UC1-AI067198-01. HH Nguyen was supported in part by Transgovernmental Enterprise for Pandemic Influenza in Korea (TEPIK) grant A103001 and National Research Foundation (NRF) grant MDNRF01251-050. International Vaccine Institute (IVI) was supported in part by grants from the governments of the Republic of Korea, Kuwait, Germany, and Sweden (Swedish International Development Cooperation Agency [SIDA]), as well as the Bill & Melinda Gates Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Injectable vaccines tend to induce systemic inflammation.

• Acute systemic inflammation tends to be associated with transient health hazards.

• Acute systemic inflammation may evolve into chronic low-grade inflammation that has been identified as a ‘silent killer’.

• Noninvasive vaccines could elicit potent protective immunity without inducing runaway systemic inflammation; hence, they tend to be safer than their injectable counterparts.

• Bioengineered nasal vaccines could confer rapid–sustained–broad protection of vaccinees against pathogens by activating discriminating arms of innate immunity as the first wave of defense, which is fortified by adaptive immunity as the second wave.

Notes