Immunogenicity and Toxicity of Different Adjuvants Can Be Characterized by Profiling Lung Biomarker Genes After Nasal Immunization.

Eita Sasaki,Keiko Furuhata,Haruka Momose,Takuo Mizukami,Hideki Asanuma,Isao Hamaguchi

doi:10.3389/fimmu.2020.02171

Eita Sasaki, Keiko Furuhata + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2020.02171

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Abstract

The efficacy of vaccine adjuvants depends on their ability to appropriately enhance the immunogenicity of vaccine antigens, which is often insufficient in non-adjuvanted vaccines. Genomic analyses of immune responses elicited by vaccine adjuvants provide information that is critical for the rational design of adjuvant vaccination strategies. In this study, biomarker genes from the genomic analyses of lungs after priming were used to predict the efficacy and toxicity of vaccine adjuvants. Based on the results, it was verified whether the efficacy and toxicity of the tested adjuvants could be predicted based on the biomarker gene profiles after priming. Various commercially available adjuvants were assessed by combining them with the split influenza vaccine and were subsequently administered in mice through nasal inoculation. The expression levels of lung biomarker genes within 24 h after priming were analyzed. Furthermore, we analyzed the antibody titer, cytotoxic T lymphocyte (CTL) induction, IgG1/IgG2a ratio, leukopenic toxicity, and cytotoxicity in mice vaccinated at similar doses. The association between the phenotypes and the changes in the expression levels of biomarker genes were analyzed. The ability of the adjuvants to induce the production of antigen-specific IgA could be assessed based on the levels of Timp1 expression. Furthermore, the expression of this gene partially correlated with the levels of other damage-associated molecular patterns in bronchoalveolar lavage fluid. Additionally, the changes in the expression of proteasome- and transporter-related genes involved in major histocompatibility complex class 1 antigen presentation could be monitored to effectively assess the expansion of CTL by adjuvants. The monitoring of certain genes is necessary for the assessment of leukopenic toxicity and cytotoxicity of the tested adjuvant. These results indicate that the efficacy and toxicity of various adjuvants can be characterized by profiling lung biomarker genes after the first instance of immunization. This approach could make a significant contribution to the development of optimal selection and exploratory screening strategies for novel adjuvants.

Highlights

Vaccines composed of purified antigens are often poorly immunogenic
Evaluation of Biomarker Gene Expression Levels From Genomic Analyses for the Prediction of WPV-Like Immunogenicity and Th1 Immunity Induced by Influenza Vaccine
We previously demonstrated that adjuvant safety in intranasal influenza vaccines can be assessed using biomarker genes sets (Table 1) [41, 43]

Summary

Introduction

Vaccines composed of purified antigens are often poorly immunogenic. The extent, strength, and duration of immune response to vaccines should be enhanced to ensure long-lived immune memory and protection. Adjuvants are substances that can enhance the immune response to vaccine antigens. The choice of adjuvant drastically affects the nature and magnitude of the adaptive immune response to vaccine antigens, primarily by affecting innate immunity [2]. The influenza split vaccine (SV) consists of hemagglutinin (HA) and neuraminidase (NA) that are present in the outer shell of influenza virus particles; the immunogenicity elicited by these is insufficient for providing protection against infection [9, 10]. R848 (resiquimod) and CpG K3 [K type CpG ODN (class B ODN)] induce Th1 immunity and enhance immunogenicity against SV vaccine antigen in mice [13,14,15]

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