After vaccination, the immune response to vaccines has to be assessed. The immune response can be analyzed by measuring the total amount of antibodies such as IgM, IgG, or IgA, usually in the serum of vaccinated patients. In the early stages of a primary antibody response, B cells secrete IgM into the blood (Clem, 2011; den Hartog et al., 2020). IgM only lasts a few weeks in the blood and detection of IgM usually indicates recent exposure to an infection or pathogen (den Hartog et al., 2020). Differentiation of B cells results in an Ig class switch recombination from IgM to IgG, IgA, or IgE (Roco et al., 2019; Siegrist, 2008). In the majority of vaccines, particularly vaccines given via the intramuscular route, B cells mainly produce IgG (den Hartog et al., 2020; Siegrist, 2008). The IgG response following vaccination can last for months or years. ELISAs are commonly used in vaccine research to measure the levels of antibodies, particularly IgM or IgG, in samples from immunized patients. Below are examples of ELISA used in malaria and coronavirus-19 (COVID-19) research to determine the antibody response following vaccination.

Malaria, a life-threatening disease caused by the Plasmodium parasite, is responsible for an estimated 229 million cases and over 409,000 deaths worldwide in 2019 (World Health Organization, 2020). Due to the severity of this disease, vaccines such as RTS,S/AS01E have been developed to reduce morbidity and mortality from malaria. RTS,S/AS01E is a virus like particle composed of the hepatitis B virus surface antigen protein and a large segment of the circumsporozoite protein (CSP) (Doban˜o, Ubillos, et al., 2019). To determine the immunogenicity of RTS,S/AS01E, studies by Doban˜o, Sanz, et al. (2019) used ELISAs to analyze CSP IgG plasma/serum concentrations following immunization of volunteers with the vaccine. CSP specific IgG levels in the samples were detected using rabbit antihuman IgG conjugated to HRP (Doban˜o, Ubillos, et al., 2019). Results showed a significant increase in IgG concentrations binding to CSP in the serum of immunized individuals and indicated that the RTS,S/AS01E vaccine produced a strong IgG response (Doban˜o, Sanz, et al., 2019). This study is an example of how ELISAs can be used to determine the immunogenicity of a vaccine.

The novel SARS-CoV-2 virus causes coronavirus disease 19 (COVID-19) (Liu et al., 2020). COVID-19 has affected over 220 countries worldwide and was responsible for over 195 million cases and 4.2 million deaths worldwide as of July 28, 2021 (World Health Organization, 2021). SARS-CoV-2 has four structural proteins including spike (S), envelope (E), membrane (M), and nucleocapsid (N) (Liu et al., 2020; Yoshimoto, 2020). The S protein and the N protein are the main immunogens. Liu et al. (2020) used an ELISA based on the recombinant SARS-CoV-2 N protein (rN) and recombinant SARS-CoV-2 S protein (rS) to detect IgM and IgG antibodies in patients who tested positive for COVID-19 (Liu et al., 2020). The rN and rS ELISAs used sandwich and competitive ELISA principles to detect IgM and IgG, respectively, in the serum of patients. Results showed an increase in IgM and IgG levels against the rN and rS proteins were detected by both ELISAs, with the highest sensitivity detected 10 days after disease onset (Liu et al., 2020). The study indicated that rN- and rS-based ELISAs could be used as a diagnostic method for detection of COVID-19 particularly 10 days after dis ease onset (Liu et al., 2020). ELISAs can be used to evaluate the immunogenicity of COVID-19 vaccines and also to assess the prevalence of COVID 19 in a population after vaccination.

References

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Clem, A. S. (2011). Fundamentals of vaccine immunology. Journal of Global Infectious Diseases, 3(1), 73 78. Available from https://doi.org/10.4103/0974-777X.77299, Wolters Kluwer Medknow Publications.

den Hartog, G., Schepp, R. M., Kuijer, M., GeurtsvanKessel, C., van Beek, J., Rots, N., Koopmans, M. P. G., van der Klis, F. R. M., & van Binnendijk, R. S. (2020). SARS-CoV 2 specific antibody detection for seroepidemiology: A multiplex analysis approach accounting for accurate seroprevalence. The Journal of Infectious Diseases, 222(9), 1452 1461. Available from https://doi.org/10.1093/infdis/jiaa479.

Doban ˜o, C., Sanz, H., Sorgho, H., Dosoo, D., Mpina, M., Ubillos, I., Aguilar, R., Ford, T., D´ ıez Padrisa, N., Williams, N. A., Ayestaran, A., Traore, O., Nhabomba, A. J., Jairoce, C., Waitumbi, J., Agnandji, S. T., Kariuki, S., Abdulla, S., Aponte, J. J., ... Daubenberger, C. (2019). Concentration and avidity of antibodies to different circumsporozoite epitopes corre late with RTS,S/AS01E malaria vaccine efficacy. Nature Communications, 10(1), 1 13.

Doban ˜o, C., Ubillos, I., Jairoce, C., Gyan, B., Vidal, M., Jime´nez, A., Santano, R., Dosoo, D., Nhabomba, A. J., Ayestaran, A., Aguilar, R., Williams, N. A., D´ ıez-padrisa, N., Lanar, D., Chauhan, V., Chitnis, C., Dutta, S., Gaur, D., Angov, E., ...Coppel, R. L. (2019). RTS, S / AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: A case-control study. BMC Medicine, 17, 157.

Liu, W., Liu, L., Kou, G., Zheng, Y., Ding, Y., Ni, W., Wang, Q., Tan, L., Wu, W., Tang, S., Xiong, Z., & Zheng, S. (2020). Evaluation of nucleocapsid and spike protein-based enzyme-linked immunosorbent assays for detecting antibodies against SARS-CoV-2. Journal of Clinical Microbiology, 58(6). Available from https://doi.org/10.1128/JCM.00461-20.

Roco, J. A., Mesin, L., Binder, S. C., Nefzger, C., Gonzalez-Figueroa, P., Canete, P. F., Ellyard, J., Shen, Q., Robert, P. A., Cappello, J., Vohra, H., Zhang, Y., Nowosad, C. R., Schiepers, A., Corcoran, L. M., Toellner, K. M., Polo, J. M., Meyer-Hermann, M., Victora, G. D., & Vinuesa, C. G. (2019). Class-switch recombination occurs infrequently in germinal centers. Immunity, 51(2), 337 350. Available from https://doi.org/10.1016/j.immuni.2019.07.001,e7.

Siegrist, C.-A. (2008). The immunology of vaccination. Vaccines (5th ed., pp. 16 34). Saunders. Available from https://www.who.int/immunization/documents/Elsevier_Vaccine_immunology.pdf

World Health Organization. (2020). World malaria report 2020: 20 years of global progress and challenges. Available from https://www.who.int/docs/default-source/malaria/world-malaria reports/9789240015791-double-page-view.pdf?sfvrsn52c24349d_5.

World Health Organization. (2021). WHO Coronavirus (COVID-19) dashboard overview data table. Available from https://covid19.who.int/.

Yoshimoto, F. K. (2020). The proteins of severe acute respiratory syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the cause of COVID-19. Protein Journal, 39(3), 198 216, Springer. Available from https://doi.org/10.1007/s10930-020-09901-4.

مواضيع ذات صلة

Antigen selection for new vaccines

Reverse vaccinology (RV) and other applications

RNA vaccines

Immunisation

DNA vaccines

Subunit vaccines

Inactivated vaccines

ANTHRAX VACCINATION

Live-attenuated vaccines

Adjuvants

New Approaches to Vaccine Development​

The Need for New Vaccines