Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia

Front Immunol. 2023 Dec 19:14:1282016. doi: 10.3389/fimmu.2023.1282016. eCollection 2023.

Abstract

Introduction: Respiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen candidate, as it is important for cell adhesion during infection. However, vaccine-associated enhanced diseases in mice, such as eosinophilic lung inflammation following RSV challenge, are a concern with G protein vaccines. This study aimed to design an effective G protein vaccine with enhanced safety and efficacy by evaluating the efficacy and adverse reactions of vaccines composed of different recombinant G proteins and adjuvants in mice.

Methods: Mice were subcutaneously immunized with glycosylated G protein expressed in mammalian cells (mG), non-glycosylated G protein expressed in Escherichia coli (eG), or F protein with or without aluminum salts (alum), CpG oligodeoxynucleotide (CpG ODN), or AddaVax. After vaccination, the levels of G-specific antibody and T-cell responses were measured. The immunized mice were challenged with RSV and examined for the viral load in the lungs and nasal turbinates, lung-infiltrating cells, and lung pathology.

Results: mG with any adjuvant was ineffective at inducing G-specific antibodies and had difficulty achieving both protection against RSV challenge and eosinophilia suppression. In particular, mG+CpG ODN induced G-specific T helper 1 (Th1) cells but only a few G-specific antibodies and did not protect against RSV challenge. However, eG+CpG ODN induced high levels of G-specific antibodies and Th1 cells and protected against RSV challenge without inducing pulmonary inflammation. Moreover, the combination vaccine of eG+F+CpG ODN showed greater protection against upper respiratory tract RSV challenge than using each single antigen vaccine alone.

Discussion: These results indicate that the efficacy of recombinant G protein vaccines can be enhanced without inducing adverse reactions by using appropriate antigens and adjuvants, and their efficacy is further enhanced in the combination vaccine with F protein. These data provide valuable information for the clinical application of G protein vaccines.

Keywords: CpG oligodeoxynucleotide; G protein; adjuvant; eosinophil; respiratory syncytial virus; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Viral
  • Eosinophilia* / prevention & control
  • GTP-Binding Proteins
  • Glycoproteins
  • Mammals
  • Mice
  • Oligodeoxyribonucleotides
  • Pneumonia*
  • Recombinant Proteins
  • Respiratory Syncytial Virus Infections*
  • Respiratory Syncytial Virus, Human*
  • Vaccines*
  • Vaccines, Combined
  • Viral Fusion Proteins

Substances

  • Antibodies, Viral
  • Viral Fusion Proteins
  • Adjuvants, Immunologic
  • Recombinant Proteins
  • Vaccines
  • GTP-Binding Proteins
  • Oligodeoxyribonucleotides
  • Glycoproteins
  • Vaccines, Combined

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number:23H02652 to YY), Japan Agency for Medical Research and Development (AMED Grant Number: JP223fa627002 to YY), the All-Osaka U Research in “The Nippon Foundation-Osaka University Project for Infectious Disease Project” (to YY), the Japan Science and Technology Agency (JST SPRING Grant Number: JPMJSP2138), and The Research Foundation for Microbial Diseases of Osaka University (BIKEN).