Inactivated rotavirus vaccine by parenteral administration induces mucosal immunity in mice

Theresa K Resch,Sung-Sil Moon,Song Li,Yuhuan Wang,Jessica Joyce,Mark Prausnitz,Baoming Jiang

doi:10.1038/s41598-017-18973-9

Abstract

To improve the safety and efficacy of oral rotavirus vaccines, we developed an inactivated rotavirus vaccine (IRV) for parenteral administration. Since it remains unknown whether parenteral vaccination can induce mucosal immunity, we performed a comprehensive assessment of immune responses to IRV in mice with an adjuvant-free dissolving polymer MN patch or by alum-adjuvanted IM injection. We demonstrated that IRV induced the expression of the gut homing receptor LPAM-1 on T and B cells in spleen and mLN of vaccinated mice. MN patch IRV vaccination induced a slight Th1 phenotype while IM vaccination induced a balanced Th1/Th2 phenotype. In addition, a dose-sparing effect was seen for rotavirus-specific serum IgG and neutralizing activity for both vaccination routes. Our study is the first to show that parenterally administered IRV can induce mucosal immunity in the gut, in addition to strong serum antibody response, and is a promising candidate vaccine in achieving global immunization against rotavirus.

Highlights

Despite the introduction of two live oral vaccines (Rotarix and RotaTeqTM) in many countries, rotavirus (RV) is still the leading cause of severe gastroenteritis and diarrhea, resulting in estimated 215,000 deaths among children under the age of 5 worldwide per year[1]
While MN patch vaccination induced a comparable level of LPAM-1-expressing B cells and T helper (Th) cells in spleen and mesenteric lymph node (mLN), IM vaccination led to a higher percentage of LPAM-1 positive B cells in mLN and more Th cells in the spleen
This is in accordance with published data that generally showed the recruitment of LPAM-1 positive memory T cells to mucosa-associated lymphoid organs[20]

Summary

Introduction

Despite the introduction of two live oral vaccines (Rotarix and RotaTeqTM) in many countries, rotavirus (RV) is still the leading cause of severe gastroenteritis and diarrhea, resulting in estimated 215,000 deaths among children under the age of 5 worldwide per year[1]. IRV CDC-9 administered by IM injection or by skin vaccination using a MN patch or device was effective in inducing IgG, IgA, homotypic and heterotypic neutralizing antibody in serum and strong protection against infection and diarrhea from oral challenge with a virulent human RV in pre-clinical studies[2,17,18,19]. It remains unknown whether parenteral vaccination can induce mucosal immunity in the intestine of animals and humans.

Methods

Results

Conclusion