Protection efficacy of mRNA-based SARS-CoV-2 variant vaccine in non-human primates

Dongrong Yi1, Yongxin Zhang1, Jing Wang1

  • 1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China.

PubMed

Insights

A novel mRNA vaccine (RG001) provides complete protection against SARS-CoV-2 variants in primates. This vaccine candidate shows broad efficacy against multiple variants, including Omicron sublineages, offering hope for controlling COVID-19.

Area of Science:

  • Virology
  • Immunology
  • Vaccine Development

Background:

  • Emergence of SARS-CoV-2 variants poses a global challenge to COVID-19 control.
  • Existing vaccines show reduced efficacy against immune-evasive variants.
  • Need for broad-spectrum countermeasures against SARS-CoV-2 and related sarbecoviruses.

Purpose of the Study:

  • To develop and evaluate a novel mRNA vaccine (RG001) encoding the full-length Spike glycoprotein of SARS-CoV-2.
  • To assess the protective efficacy of RG001 against SARS-CoV-2 variants in a non-human primate model.
  • To investigate the neutralizing antibody and cellular immune responses elicited by RG001.

Main Methods:

  • Development of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (RG001).
  • Intramuscular immunization of Rhesus monkeys with two doses of RG001.
  • Assessment of neutralizing antibodies, cellular responses, viral replication, and lung lesions in immunized animals post-challenge.
  • Evaluation of a third dose of RG001 in mice against Omicron variants (BA.1, XBB.1.16, JN.1).

Main Results:

  • Two doses of RG001 conferred complete protection in Rhesus monkeys, preventing acute lung lesions and viral replication.
  • RG001 elicited robust neutralizing antibodies and cellular responses against SARS-CoV-2 variants.
  • A third dose of RG001 demonstrated effective neutralizing antibodies against epidemic strains XBB and JN.1.
  • Similar cellular responses were observed against SARS-CoV-2 Omicron variants in immunized mice.

Conclusions:

  • RG001, an mRNA-LNP vaccine, shows significant potential for broad protection against SARS-CoV-2 and its variants.
  • The vaccine candidate effectively induces humoral and cellular immunity, crucial for combating immune-evasive strains.
  • RG001 represents a promising countermeasure for controlling the ongoing COVID-19 pandemic.