Optimization process of vaccine production of outer membrane vesicle from Neisseria meningitidis associated with Zika virus





OMV; Zika Virus; Vaccine; Outer membrane vesicle; Scheduling.


Several vaccine prototypes were made using variations in concentration, volume, time and speed of agitation. From these prototypes, some characterization assays were carried out, such as the analysis of particle size and zeta potential, where it was possible to determine the size of the nanoparticles, the polydispersity index, with the most promising samples having a size of 252.1nm ± 71.2 nm. The polydispersity index was 0.572 ±0.02, the standard deviation being a little high due to the presence of free viral particles and some associated vesicles. It is noteworthy that the isolated vesicle has a size of 140 to 160nm and the polydispersity index of 0.513 demonstrates that we do not have interference in the sample of our vesicle (it is known that the size of the viral particle of Zika virus is between 40 and 60nm). Cytotoxicity testing was done to analyze whether they have cytotoxic profiles and also demonstrate that the prototype's neutralization and inactivation method works correctly. The analysis of the protein profile of some of the samples revealed that there are two major Zika virus proteins in the fused proteasome, namely the E protein, which is directly involved in the recognition of host cell receptors, and the C protein, which is related to capsid assembly, in addition to playing an important role in the immune response.


Agumadu, V. C., & Ramphul, K. (2018). Zika Virus: A Review of Literature. Cureus, 10(7), e3025. https://doi.org/10.7759/cureus.3025

Alves, D.A., Mattos, I.B., Hollanda, L.M., & Lancellotti, M. (2013). Use of Mesoporous Silica SBa-15 and SBa-16 in Association of Outer Membrane Vesicles - OMV from Neisseria meningitidis. Journal of Vaccines and Vaccination, 2013, 1-6.

Amaral P., Resende de Carvalho L., Hernandes Rocha T.A., da Silva N.C. & Vissoci J.R.N. (2019) Geospatial modeling of microcephaly and zika virus spread patterns in Brazil. PLOS ONE 14(9): e0222668.

Barrett, A.D.T. (2018) Current status of Zika vaccine development: Zika vaccines advance into clinical evaluation. npj Vaccines 3, 24.

Barreto-Vieira, D. F., Barth, O. M., Silva, M. A. N. da., Santos, C. C., Santos, A. da S., F Filho, J. B., & Filippis, A. M. B. de. (2016). Ultrastructure of Zika virus particles in cell cultures. Memórias Do Instituto Oswaldo Cruz, 111(Mem. Inst. Oswaldo Cruz, 2016 111(8)), 532–534. https://doi.org/10.1590/0074-02760160104

Chen, Y., Chi, X., Zhang, H., Zhang, Y., Qiao, L., Ding, J., Han, Y., Linm Y. & Jiang, J. (2023). Identification of Potent Zika Virus NS5 RNA-Dependent RNA Polymerase Inhibitors Combining Virtual Screening and Biological Assays. International Journal of Molecular Sciences, 24(3), 1900. MDPI AG. Retrieved from http://dx.doi.org/10.3390/ijms24031900

Cruz-Oliveira, C., Freire, J. M., Conceição, T. M., Higa, L. M., Castanho, M. A., & Da Poian, A. T. (2015). Receptors and routes of dengue virus entry into the host cells. FEMS microbiology reviews, 39(2), 155–170. https://doi.org/10.1093/femsre/fuu004

Dai, L., Song, J., Lu, X., Deng, Y. Q., Musyoki, A. M., Cheng, H., Zhang, Y., Yuan, Y., Song, H., Haywood, J., Xiao, H., Yan, J., Shi, Y., Qin, C. F., Qi, J., & Gao, G. F. (2016). Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody. Cell host & microbe, 19(5), 696–704. https://doi.org/10.1016/j.chom.2016.04.013

Garcez, P. P., Loiola, E. C., Madeiro da Costa, R., Higa, L. M., Trindade, P., Delvecchio, R., Nascimento, J. M., Brindeiro, R., Tanuri, A., & Rehen, S. K. (2016). Zika virus impairs growth in human neurospheres and brain organoids. Science (New York, N.Y.), 352(6287), 816–818. https://doi.org/10.1126/science.aaf6116

Giraldo, M. I., Gonzalez-Orozco, M., & Rajsbaum, R. (2023). Pathogenesis of Zika Virus Infection. Annual review of pathology, 18, 181–203. https://doi.org/10.1146/annurev-pathmechdis-031521-034739

Gurumayum, S., Brahma, R., Naorem, L. D., Muthaiyan, M., Gopal, J., & Venkatesan, A. (2018). ZikaBase: An integrated ZIKV- Human Interactome Map database. Virology, 514, 203–210. https://doi.org/10.1016/j.virol.2017.11.007

Labib, B. A., & Chigbu, D. I. (2022). Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases. Tropical Medicine and Infectious Disease, 7(6), 106. MDPI AG. Retrieved from http://dx.doi.org/10.3390/tropicalmed7060106

Lee, J., & Shin, O. (2019). Advances in Zika Virus–Host Cell Interaction: Current Knowledge and Future Perspectives. International Journal of Molecular Sciences, 20(5), 1101. MDPI AG. Retrieved from http://dx.doi.org/10.3390/ijms20051101

Markoff, L. (2003) 5′-and 3′-noncoding regions in Flavivirus RNA. ISSN 0065-3527

Martins, P., Machado, D., Theizen, T. H., Guarnieri, J. P. O., Bernardes, B. G., Gomide, G. P., Corat, M. A. F., Abbehausen, C., Módena, J. L. P., Melo, C. F. O. R., Morishita, K. N., Catharino, R. R., Arns, C. W., & Lancellotti, M. (2018). Outer Membrane Vesicles from Neisseria Meningitidis (Proteossome) Used for Nanostructured Zika Virus Vaccine Production. Scientific reports, 8(1), 8290. https://doi.org/10.1038/s41598-018-26508-z

Pang, Z., Chong, J., Zhou, G., Morais D., Chang, L., Barrette, M., Gauthier, C., Jacques, PE., Li, S., and Xia, J. (2021) MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights Nucl. Acids Res. (doi: 10.1093/nar/gkab382)

Pattnaik, A., Sahoo, B. R., & Pattnaik, A. K. (2020). Current Status of Zika Virus Vaccines: Successes and Challenges. Vaccines, 8(2), 266.

Roby, J. A., Setoh, Y. X., Hall, R. A., & Khromykh, A. A. (2015). Post-translational regulation and modifications of flavivirus structural proteins. The Journal of general virology, 96(Pt 7), 1551–1569. https://doi.org/10.1099/vir.0.000097

van der Pol, L., Stork, M., & van der Ley, P. (2015). Outer membrane vesicles as platform vaccine technology. Biotechnology journal, 10(11), 1689–1706. https://doi.org/10.1002/biot.201400395

World Health Organization. The history of zika virus (2016). https://www.who.int/news-room/feature-stories/detail/the-history-of-zika-virus

Yeasmin M., Molla M.M.A., Masud H.M.A.A., Saif-Ur-Rahman K.M. (2023) Safety and immunogenicity of Zika virus vaccine: a systematic review of clinical trials. Rev Med Virol; 33(1): e2385. https://doi.org/10.1002/rmv.2385

Zhang, Y., Corver, J., Chipman, P. R., Zhang, W., Pletnev, S. V., Sedlak, D., Baker, T. S., Strauss, J. H., Kuhn, R. J., & Rossmann, M. G. (2003). Structures of immature flavivirus particles. The EMBO journal, 22(11), 2604–2613. https://doi.org/10.1093/emboj/cdg270




How to Cite

GUARNIERI, J. P. de O. .; BERNARDES, B. G.; SILVA, C. F. M. da .; ATAIDE, J. A.; OLIVEIRA, A. N. de .; DELAFIORI, J.; CATHARINO, R. R.; MAZZOLA, P. G.; LACELLOTTI, M. Optimization process of vaccine production of outer membrane vesicle from Neisseria meningitidis associated with Zika virus. Research, Society and Development, [S. l.], v. 12, n. 4, p. e25912441268, 2023. DOI: 10.33448/rsd-v12i4.41268. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/41268. Acesso em: 6 jun. 2023.



Agrarian and Biological Sciences