Safety and immunogenicity of a SARS-CoV-2 recombinant protein subunit vaccine adjuvanted with Alum + CpG 1018 in healthy Indonesian adults: A multicenter, randomized, comparative, observer-blind, placebo-controlled phase 2 study

Hum Vaccin Immunother. 2024 Dec 31;20(1):2429231. doi: 10.1080/21645515.2024.2429231. Epub 2024 Dec 5.

Abstract

Globally, dozens of COVID-19 vaccines are licensed under emergency or conditional authorization, but especially in low and middle-income countries, their availability varies. Indonesia decided to become independent and produce its own vaccines locally. This study investigated the safety and immunogenicity of a SARS-CoV-2 recombinant protein subunit vaccine adjuvanted with Alum + CpG 1018. This study involved 360 adults aged 18 years and above. It compared two vaccine dosages, a-12.5 µg and a 25-µg dose of receptor binding domain protein, to a placebo (1:1:1). A total of 40.6% of participants in this study experienced at least one adverse event (AE), with most being mild. There was no statistically significant difference in AEs between the groups. The microneutralization test showed the highest neutralizing antibody titer (IU/mL) in the 25 µg dose vaccine group at day 28 after the second dose (3,300 95%CI 2,215-4,914), although it was not statistically different from the 12.5 µg dose group (3,157 95%CI 2,135-4,669). Similarly, IgG antibody concentrations in the 25 µg dose vaccine group at day 28 were the highest compared to the 12.5 µg dose and placebo. According to protocol, only the formulation with the better antibody profile and comparable reactogenicity was further evaluated at months three and six. Thus, follow-up was only performed for the 25 µg dose vaccine, demonstrating antibody persistence at month six and had a favorable safety profile. These results position this SARS-CoV-2 recombinant protein subunit vaccine adjuvanted with Alum + CpG 1018 as a promising candidate to fight against COVID-19.

Keywords: Covid-19; SARS-CoV-2; immunogenicity; recombinant protein subunit vaccine; safety.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Clinical Trial, Phase II
  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic* / administration & dosage
  • Adjuvants, Immunologic* / adverse effects
  • Adjuvants, Vaccine / administration & dosage
  • Adolescent
  • Adult
  • Alum Compounds* / administration & dosage
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral* / blood
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / adverse effects
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Indonesia
  • Male
  • Middle Aged
  • Oligodeoxyribonucleotides* / administration & dosage
  • Oligodeoxyribonucleotides* / adverse effects
  • Oligodeoxyribonucleotides* / immunology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • SARS-CoV-2* / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology
  • Young Adult

Substances

  • 1018 oligonucleotide
  • Adjuvants, Immunologic
  • Adjuvants, Vaccine
  • Alum Compounds
  • aluminum sulfate
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Vaccines, Subunit

Grants and funding

Bio Farma supported this work [Grant No. 019.21/DIR/II/2022, PO/BIOF/2022/0951, PO-00036326].