Study of the immunogenicity, efficacy and safety of recombinant RBD SARS-CoV-2 vaccine with CpG adjuvant in rodent, non-rodent and Maccaca fascicularis using Indonesian Strain Virus

Limeilati, N. A.; Nidom, R. V.; Sari, T. T.; Kusumarahayu, N. P.; Fransiska, S. V.; Indrasari, S.; Garmana, A. N.; Ayuningtyas, D. K.; Nugroho, G. S.; Darsono,; Maharani,; Wijayadikusumah, A. R.; Sukandar, E. Y.; Nidom, A. N.; Adnyana, I. K.; Nurainy, N.; Nidom, C.

doi:10.1101/2024.12.18.629000

bioRxiv · 10.1101/2024.12.18.629000

Study of the immunogenicity, efficacy and safety of recombinant RBD SARS-CoV-2 vaccine with CpG adjuvant in rodent, non-rodent and Maccaca fascicularis using Indonesian Strain Virus

Limeilati, N. A.·Nidom, R. V.·Sari, T. T.·Kusumarahayu, N. P.·Fransiska, S. V.·Indrasari, S.·Garmana, A. N.·Ayuningtyas, D. K.·Nugroho, G. S.·Darsono,·Maharani,·Wijayadikusumah, A. R.·Sukandar, E. Y.·Nidom, A. N.·Adnyana, I. K.·Nurainy, N.·Nidom, C.

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Abstract

SARS-CoV-2 is the leading cause of the COVID-19 pandemic that causes acute respiratory syndrome, emerged in late 2019, and was declared a global pandemic on March 11th, 2020. A safe and effective vaccine that prevents SARS-CoV-2 infection or minimize SARS-CoV-2 disease burden is needed. However, in 2021, Low- and middle-income countries (LMICs) face challenges regarding supply of COVID-19 vaccines. Indonesia, as a public sector vaccine manufacturing in developing countries was developed COVID-19 vaccine using a platform based on recombinant subunit proteins, a Receptor Binding Domain (RBD) of SARS-CoV-2 formulated with combination of Alhydrogel and CpG Oligodeoxynucleotides 1018 (CpG). In this study, we report the preclinical study including immunogenicity, toxicity and efficacy of vaccine in animal models. The vaccine immunogenicity tested in mice and non-human primates, the toxicity was done in rodents and non-rodents and challenged study and efficacy was done in non-human primates (NHPs) model. The animal model was vaccinated intramuscularly (IM). The serology result in mice and non-human primates showed significant antibody titers and neutralizing antibody responses compared to the RBD formulations adjuvanted with Alhydrogel only. Safety study in Wistar rats and New Zealand rabbits for single-dose (acute toxicity) and repeated-dose (sub-chronic toxicity) showed no abnormalities in the animals organs and behaviors and no deaths were reported in tested animals. Two doses of vaccination have been shown to protect NHPs against SARS-CoV-2 infection, as detected by drastic viral reduction from sample swab in nasal, anal, trachea and nasal wash in 7 days after virus challenged, also viral load measurement from lung and BAL tissue showed negative result, which gave better result than negative control and control vaccine group. No evidence of disease enhancement was observed. These results support clinical development of SARS-CoV-2 vaccine, and in 2022 this vaccine has been approved for emergency use in Indonesia.

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Limeilati, N. A., Nidom, R. V., Sari, T. T., Kusumarahayu, N. P., Fransiska, S. V., Indrasari, S., Garmana, A. N., Ayuningtyas, D. K., Nugroho, G. S., Darsono,, Maharani,, Wijayadikusumah, A. R., Sukandar, E. Y., Nidom, A. N., Adnyana, I. K., Nurainy, N., Nidom, C.. 2024-12-20. Study of the immunogenicity, efficacy and safety of recombinant RBD SARS-CoV-2 vaccine with CpG adjuvant in rodent, non-rodent and Maccaca fascicularis using Indonesian Strain Virus. https://doi.org/10.1101/2024.12.18.629000

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