Immunogenicity of inactivated rotavirus in rhesus monkey, and assessment of immunologic mechanisms

Hum Vaccin Immunother. 2023 Dec 31;19(1):2189598. doi: 10.1080/21645515.2023.2189598. Epub 2023 Mar 30.

Abstract

Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine is of great significance for preventing rotavirus infection and reducing severe mortality. The current study aimed to develop and evaluate the immunogenicity of inactivated rotavirus vaccine (IRV) in rhesus monkeys. Monkeys received two or three IRV injections intramuscularly at a 4-week interval. Neutralizing antibodies, cellular immunity, PBMC gene expression profiling, and immune persistence were evaluated. Three-dose immunization of IRV induced a higher level of neutralizing, IgG and IgA antibodies compared to two-dose immunization. IRV induced IFN-γ secretion to mediate cellular immune responses, including robust pro-inflammatory and antiviral responses. Chemokine-mediated signaling pathways and immune response were broadly activated by IRV injection. The IRV-induced neutralizing antibodies resulting from two doses returned to baseline levels 20 weeks after full immunization, while those resulting from three doses returned to baseline levels 44 weeks after full immunization. Increasing immunization dose and injection number will help to improve IRV immunogenicity and neutralizing antibody persistence.

Keywords: Rotavirus; immunogenicity; immunologic mechanism; inactivated rotavirus vaccine; rhesus monkey.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Leukocytes, Mononuclear
  • Macaca mulatta
  • Rotavirus Infections* / prevention & control
  • Rotavirus Vaccines*
  • Rotavirus*
  • Vaccines, Inactivated

Substances

  • Antibodies, Viral
  • Rotavirus Vaccines
  • Antibodies, Neutralizing
  • Vaccines, Inactivated

Grants and funding

This work was supported by the [Major Science and Technology Special Project of Yunnan Province (Biomedicine) #1] under Grant [number 202202AA100006]; [Science and Technology Project of Yunnan Province—general program #2] under Grant [number 202201AT070236]; [CAMS Innovation Fund for Medical Sciences (CIFMS) #3] under Grant [number 2021-I2M-1-043]; [Science and Technology Project of Yunnan Province—general program #4] under Grant [number 2019FB020]; and [Yunnan Province Innovative Vaccine Technology and Industrial Transformation Platform #5] under Grant [number 202002AA100009].