Author(s): Eugenia Citta Nirmala, Sri Agus Sudjarwo, Suryo Kuncorojakti, Heni Puspitasari, Rofiqul A’la, Andi Yasmin Wijaya, Helen Susilowati, Diyantoro, Nusdianto Triakoso6, Boedi Setiawan, Agung Eru Wibowo, Fedik Abdul Rantam


DOI: 10.52711/0974-360X.2023.00469   

Address: Eugenia Citta Nirmala1, Sri Agus Sudjarwo2, Suryo Kuncorojakti3,4, Heni Puspitasari4, Rofiqul A’la4, Andi Yasmin Wijaya4, Helen Susilowati4, Diyantoro4,5, Nusdianto Triakoso6,Boedi Setiawan7, Agung Eru Wibowo8, Fedik Abdul Rantam4,9*
1Master’s Student, Faculty of Veterinary Medicine, Airlangga University, Surabaya, East Java, 60115, Indonesia.
2Pharmacology Laboratory, Division of Basic Veterinary Science, Faculty of Veterinary Medicine, Airlangga University, Surabaya, East Java, 60115, Indonesia.
3Histology Laboratory, Division of Veterinary Anatomy, Faculty of Veterinary Medicine, Airlangga University, Surabaya, East Java, 60115, Indonesia.
4Research Center for Vaccine Technology and Development, Institute of Tropical Disease, Airlangga University, Surabaya, East Java, 60115, Indonesia.
5Department of Health Science, Faculty of Vocational Studies, Airlangga University, Surabaya, East Java, 60115, Indonesia.
6Internal Medicine Department, Airlangga University Animal Hosp

Published In:   Volume - 16,      Issue - 6,     Year - 2023

Vaccination is deemed the best approach against the COVID-19 pandemic. In regard of safety and protectivity, the whole inactivated vaccine platform is advantageous and widely used. Whole inactivated vaccine provides broader protection against various antigenic components of SARS-CoV-2. This study aims to analyze the immune response of cynomolgus macaques (Macaca fascicularis) following inactivated SARS-CoV-2 vaccine administration. The analysis utilized the flow cytometry and enzyme-linked immunosorbent assay to evaluate CD59 NK cell expression and serum IL-6 level. This research used 6 macaques which were divided into 2 groups: Adult and Adolescence. Each group was consisted of 3 macaques. The macaques received two doses of 3 µg of inactivated SARS-CoV-2 vaccine with 21 days interval between first and second dose. CD59 and IL-6 level were measured before the first vaccination (D0), 21 days post-vaccination but before second dose (D21), and 14 days after the second dose (D35). The result showed significant escalation (p = 0.05) of CD59 NK cell expression between D0, D21, and D35 in both adult and adolescence macaques. Higher expression of CD59 NK cell was found in adult macaques compared to adolescence macaques. Meanwhile, the level of IL-6 remained constant (p > 0.05) throughout D0, D21, and D35 in both groups. In conclusion, the inactivated SARS-CoV-2 vaccine candidate can increase CD59 NK cell expression significantly, while IL-6 level was mildly elevated although the differences were insignificant.

Cite this article:
Eugenia Citta Nirmala, Sri Agus Sudjarwo, Suryo Kuncorojakti, Heni Puspitasari, Rofiqul A’la, Andi Yasmin Wijaya, Helen Susilowati, Diyantoro, Nusdianto Triakoso6,Boedi Setiawan, Agung Eru Wibowo, Fedik Abdul Rantam. The response of CD59 NK cell and IL-6 level in Cynomolgus macaque immunized with inactivated SARS-CoV-2 vaccine candidate. Research Journal of Pharmacy and Technology 2023; 16(6):2847-3. doi: 10.52711/0974-360X.2023.00469

Eugenia Citta Nirmala, Sri Agus Sudjarwo, Suryo Kuncorojakti, Heni Puspitasari, Rofiqul A’la, Andi Yasmin Wijaya, Helen Susilowati, Diyantoro, Nusdianto Triakoso6,Boedi Setiawan, Agung Eru Wibowo, Fedik Abdul Rantam. The response of CD59 NK cell and IL-6 level in Cynomolgus macaque immunized with inactivated SARS-CoV-2 vaccine candidate. Research Journal of Pharmacy and Technology 2023; 16(6):2847-3. doi: 10.52711/0974-360X.2023.00469   Available on:

1.    Rantam, F. A., Prakoeswa, C. R., Tinduh, D., Nugraha, J., Susilowati, H., Wijaya, A. Y., Puspaningsih, N. N., Puspitasari, D., Husada, D., Kurniati, N. D., and Aryati, A. Characterization of SARS-COV-2 east java isolate, Indonesia. F1000Research. 2021; 10: 480.
2.    Gubernatorova, E. O., Gorshkova, E. A., Polinova, A. I. and Drutskaya, M. S. IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine & Growth Factor Reviews. 2020; 53: 13–24.
3.    Khailany, R. A., Safdar, M. and Ozaslan, M. Genomic characterization of a novel SARS-CoV-2. Gene Reports. 2020; 19: 100682.
4.    Singhal, T. (2020). A review of Coronavirus Disease-2019 (COVID-19). The Indian Journal of Pediatrics. 87(4), 281–286.
5.    Naresh, B. V. A review of the 2019 novel coronavirus (covid-19) pandemic. Asian Journal of Pharmaceutical Research. 2020; 10(3): 233.
6.    Jain, M. S., and Barhate, S. D. Corona viruses are a family of viruses that range from the common cold to mers corona virus: A Review. Asian Journal of Research in Pharmaceutical Science. 2020; 10(3): 204.
7.    Acuti Martellucci, C., Flacco, M. E., Cappadona, R., Bravi, F., Mantovani, L. and Manzoli, L. SARS-CoV-2 pandemic: An overview. Advances in Biological Regulation. 2020; 77: 100736.
8.    Kumar Balai, M. UK variant COVID-19. Asian Journal of Nursing Education and Research. 2021; 601–604.
9.    Rantam, F. A., Kharisma, V. D., Sumartono, C., Nugraha, J., Wijaya, A. Y., Susilowati, H., Kuncorojakti, S., and Nugraha, A. P. Molecular docking and dynamic simulation of conserved B cell epitope of SARS-COV-2 glycoprotein Indonesian isolates: An immunoinformatic approach. F1000Research. 2021; 10: 813.
10.    Al-Hamamy, H. R. Covid-19: Immune response. Research Journal of Pharmacy and Technology. 2022; 15 (1); 467–470.
11.    B. Chavan, M., Tarade, D., H. Pagare, K., and S. Jain, R. A review on coronavirus. Research Journal of Science and Technology. 2021; 253–255.
12.    Wu, Y. C., Chen, C. S. and Chan, Y. J. The outbreak of COVID-19: An overview. Journal of the Chinese Medical Association. 2020; 83(3): 217–220.
13.    Dhar Chowdhury, S. and Oommen, A. M. Epidemiology of covid-19. Journal of Digestive Endoscopy. 2020; 11(01): 03–07.
14.    Yuki, K., Fujiogi, M. and Koutsogiannaki, S. Covid-19 pathophysiology: A Review. Clinical Immunology. 2020; 215: 108427.
15.    Gade, A., Sawant, R., Parkar, S., and Kegade, P. SARS-COV-2 the beta genome coronavirus: A brief overview, pathogenesis and treatment. Asian Journal of Research in Pharmaceutical Science. 2020; 10(4): 299–310.
16.    Fitriah, M., Agustina Tambunan, B., Kahar, H., Nugraha, J., Arinil Aulia, F., Aryati, A., Yudhawati, R., Sudarsono, S., Tinduh, D., Sigit Prakoeswa, C. R., and Hernaningsih, Y. Characteristics of natural killer (NK) cell and T lymphocyte in COVID-19 patients in Surabaya. Indonesia. Research Journal of Pharmacy and Technology. 2022; 2198–2203.
17.    Bhattacharjee, A., Randhoni Chanu, N., and Bhattacharya, K. Covid-19 pandemic: A pragmatic plan for therapeutic intervention. Research Journal of Pharmacy and Technology. 2022; 2862–2868.
18.    Yao, Y. F., Wang, Z. J., Jiang, R. D., Hu, X., Zhang, H. J., Zhou, Y. W., Gao, G., Chen, Y., Peng, Y., Liu, M. Q., Zhang, Y. N., Min, J., Lu, J., Gao, X. X., Guo, J., Peng, C., Shen, X. R., Li, Q., Zhao, K., Yang, L. Wan, X., Zhang, B., Huang, W. H., Wu, J., Zhou, P., Yang, X. L., Shen, S., Shan, C.,Yuan, Z. M. and Shi, Z. L. Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates. Virologica Sinica. 2021; 36(5): 879–889.
19.    Jara, A., Undurraga, E. A., González, C., Paredes, F., Fontecilla, T., Jara, G., Pizarro, A., Acevedo, J., Leo, K., Leon, F., Sans, C., Leighton, P., Suárez, P., García-Escorza, H., and Araos, R. Effectiveness of an inactivated SARS-COV-2 vaccine in Chile. New England Journal of Medicine. 2021; 385(10): 875–884.
20.    Gupta, R. The management of Coronavius pandemic 2019-2020. Asian Journal of Pharmaceutical Research. 2022; 10(4): 327–330.
21.    Pollard, A.J. and Bijker, E.M. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2020; 21: 83–100 .
22.    Shehzad, A., Tacharina, M. R., Kuncorojakti, S., Ahmad, H. I., A’la, R., Wijaya, A. Y., Tyasningsih, W., and Rantam, F. A.  Molecular characterization and prediction of B-cell epitopes for the development of SARS-COV-2 vaccine through bioinformatics approach. Journal of Pharmacy & Pharmacognosy Research. 2022; 10(3): 429–444.
23.    Kumbhar, R. P., Suryawanshi, S. S., Patil, P. P., and V. Patil, S.  An opportunities and challenges in vaccine development. Asian Journal of Research in Pharmaceutical Sciences. 2022; 83–87.
24.    Zhang, J., Zeng, H., Gu, J., Li, H., Zheng, L. and Zou, Q.  Progress and prospects on vaccine development against SARS-COV-2. Vaccines. 2022; 8(2): 153.
25.    Dong, Y., Dai, T., Wei, Y. et al. A systematic review of SARS-CoV-2 vaccine candidates. Sig Transduct Target Ther. 2020; 5:, 237.
26.    Wagstaffe, H. R., Mooney, J. P., Riley, E. M. and Goodier, M. R. Vaccinating for natural killer cell effector functions. Clinical & Translational Immunology. 2018; 7(1):
27.    Prager, I., and Watzl, C. Mechanisms of Natural Killer cell‐mediated cellular cytotoxicity. Journal of Leukocyte Biology. 2019; 105(6): 1319–1329.
28.    Pishesha, N., Harmand, T. J., Rothlauf, P. W., Praest, P., Alexander, R. K., van den Doel, R., Liebeskind, M. J., Vakaki, M. A., McCaul, N., Wijne, C., Verhaar, E., Pinney, W., Heston, H., Bloyet, L.-M., Pontelli, M. C., Ilagan, M. X., Jan Lebbink, R., Buchser, W. J., Wiertz, E. J., Whelan, S. P. J. and Ploegh, H. L.  A class II MHC-targeted vaccine elicits immunity against SARS-COV-2 and its variants. Proceedings of the National Academy of Sciences. 2021; 118(44).
29.    Farahani, M., Niknam, Z., Mohammadi Amirabad, L., Amiri-Dashatan, N., Koushki, M., Nemati, M., Andesh Pouya, F., Rezaei-Tavirani, M., Rasmi, Y. and Tayebi, L. Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets. Biomedicine & Pharmacotherapy. 2022; 145: 112420.
30.    Velazquez-Salinas, L., Verdugo-Rodriguez, A., Rodriguez, L. L. and Borca, M. V. The role of interleukin 6 during viral infections. Frontiers in Microbiology. 2019; 10.
31.    Eto, D., Lao, C., DiToro, D., Barnett, B., Escobar, T. C., Kageyama, R., Yusuf, I. and Crotty, S. Il-21 and IL-6 are critical for different aspects of B cell immunity and redunandtly induce optimal follicular helper CD4 T cell (tfh) differentiation. PLoS ONE. 2011;  6(3).
32.    Steensels, D., Pierlet, N., Penders, J., Mesotten, D. and Heylen, L.  Comparison of SARS-COV-2 antibody response following vaccination with BNT162B2 and mRNA-1273. JAMA. 2021; 326(15): 1533.
33.    Guo, H., Zhang, H., Lu, L., Ezzelarab, M. B., and Thomson, A. W. Generation, cryopreservation, function and in vivo persistence of ex vivo expanded cynomolgus monkey regulatory T cells. Cellular Immunology. 2015; 295(1): 19–28.
34.    Dworacki, G., Sikora, J., Mizera-Nyczak, E., Trybus, M., Mozer-Lisewska, I., Czyz, A. and Zeromski, J. Flow cytometric analysis of CD55 and CD59 expression on blood cells in paroxysmal nocturnal haemoglobinuria. Folia Histochemica Et Cytobiologica. 2005; 43(2): 117–120.
35.    Mahmoud, H. H., Nasef, N. M., Eldewi, D. M. and Galal, R. K. Role of complement regulatory proteins  (CD55, CD59, and CD35) on red blood cells of β-thalassaemia patients. Open Journal of Blood Diseases. 2021; 11(04): 89–104.
36.    Perwitasari-Farajallah, D. and Farajallah, A. Testing Reliability of Serum Samples as a DNA Source on Captive Breeding Monkeys. BIOTROPIA. 2014; 21(2): 125-130.
37.    Farsakoglu, Y., Palomino-Segura, M., Latino, I., Zanaga, S., Chatziandreou, N., Pizzagalli, D. U., Rinaldi, A., Bolis, M., Sallusto, F., Stein, J. V. and Gonzalez, S. F. Influenza vaccination induces NK-cell-mediated type-II IFN response that regulates humoral immunity in an il-6-dependent manner. Cell Reports. 2019;  26(9).
38.    Paust, S., Senman, B. anda Von Andrian, U. H. Adaptive immune responses mediated by Natural Killer Cells. Immunological Reviews. 2010; 235(1): 286–296.
39.    Chester, C., Fritsch, K., and Kohrt, H. E. Natural killer cell immunomodulation: Targeting activating, inhibitory, and co-stimulatory receptor signaling for cancer immunotherapy. Frontiers in Immunology. 2015; 6.
40.    Hazeldine, J. and Lord, J. M. The impact of ageing on Natural Killer cell function and potential consequences for health in older adults. Ageing Research Reviews. 2013; 12(4): 1069–1078.
41.    Magro, G. SARS-COV-2 and COVID-19: Is interleukin-6 (IL-6) the ‘culprit lesion’ of ARDS onset? what is there besides tocilizumab? SGP130FC. Cytokine: X. 2020; 2(2): 100029.
42.    Hodes, G. E., Ménard, C. and Russo, S. J. Integrating interleukin-6 into depression diagnosis and treatment. Neurobiology of Stress. 2016;  4: 15–22.
43.    Khalife, J., Ghose, J., Martella, M., Viola, D., Rocci, A., Troadec, E., Terrazas, C., Satoskar, A. R., Gunes, E. G., Dona, A., Sanchez, J. F., Bergsagel, P. L., Chesi, M., Pozhitkov, A., Rosen, S., Marcucci, G., Keats, J. J., Hofmeister, C. C., Krishnan, A., Caserta, E. and Pichiorri, F. Mir-16 regulates crosstalk in NF-ΚB tolerogenic inflammatory signaling between myeloma cells and bone marrow macrophages. JCI Insight. 2019; 4(21):
44.    Yousif, A. S., Ronsard, L., Shah, P., Omatsu, T., Sangesland, M., Bracamonte Moreno, T., Lam, E. C., Vrbanac, V. D., Balazs, A. B., Reinecker, H.-C. and Lingwood, D. The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells. Immunity. 2021; 54(2).
45.    Bensussen, A., Álvarez-Buylla, E. R., and Díaz, J. SARS-COV-2 NSP5 protein causes acute lung inflammation, a dynamical mathematical model. Frontiers in Systems Biology. 2021; 1.
46.    Sekiya, T., Mifsud, E. J., Ohno, M., Nomura, N., Sasada, M., Fujikura, D., Daito, T., Shingai, M., Ohara, Y., Nishimura, T., Endo, M., Mitsumata, R., Ikeda, T., Hatanaka, H., Kitayama, H., Motokawa, K., Sobue, T., Suzuki, S., Itoh, Y., Brown, L. E., Ogasawara, K., Kino, Y. and Kida, H. Inactivated whole virus particle vaccine with potent immunogenicity and limited IL-6 induction is ideal for influenza. Vaccine. 2019; 37(15): 2158–2166.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available