AAV-expressed G protein induces robust humoral and cellular immune response and provides durable protection from rabies virus challenges in mice

Vet Microbiol. 2020 Mar:242:108578. doi: 10.1016/j.vetmic.2020.108578. Epub 2020 Jan 11.

Abstract

Rabies is a highly lethal infectious zoonosis caused by rabies virus (RABV), and the mortality rate is almost 100 % once clinical symptoms appear, which poses a huge threat to public health security across the many parts of the word. Vaccination is reported to be the most effective approach to prevent the disease. G protein is the only protein present on the surface of RABV, it also could induce humoral immunity to produce virus neutralizing antibodies (VNA) and stimulate T cells to produce cellular immunity. Adeno-associated viruses (AAVs) have been used as vectors for gene therapy of different human diseases for its low immunogenicity, high safety and long-term stable expression. To develop a safe and effective vaccine, recombinant AAVs containing different kind of G gene were constructed. After intramuscular (i.m.) immunization in mice, all of these rAAV-G vaccines could induce the production of high levels of VNA and effective cellular immune response. Consistently, all of the rAAV-G vaccines could provide protection against lethal RABV challenge. Our results shown that the rAAV-G vaccines could be potential candidates used in the control of RABV infection. In addition, rAAV-G as a vaccine has many advantages of low preparation cost, simple storage and transportation conditions (4 °C storage and transportation), simple immunization program (only one immunization) and so on. Thence, the rAAV-G vaccines could be potential candidates used in the control of RABV infection.

Keywords: Adeno-associated viruses (AAVs); Glycoprotein; Rabies virus (RABV); Vaccine.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Dependovirus / genetics
  • Dependovirus / immunology
  • Female
  • Immunity, Cellular*
  • Immunity, Humoral*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Rabies / immunology
  • Rabies / prevention & control*
  • Rabies Vaccines / genetics
  • Rabies Vaccines / immunology*
  • Rabies virus / genetics
  • Rabies virus / immunology
  • Vaccination
  • Viral Proteins / genetics
  • Viral Proteins / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Membrane Glycoproteins
  • Rabies Vaccines
  • Viral Proteins