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. 2022 Jun 17;14(6):1328.
doi: 10.3390/v14061328.

Human Intramuscular Hyperimmune Gamma Globulin (hIHGG) Anti-SARS-CoV-2-Characteristics of Intermediates and Final Product

Elzbieta Lachert  1 , Joanna Lasocka  1 , Artur Bielawski  2 , Ewa Sulkowska  3 , Katarzyna Guz  4 , Krzysztof Pyrc  5 , Agnieszka Dabrowska  5   6 , Agata Wawryniuk-Malmon  2 , Magdalena Letowska  1 , Krzysztof Tomasiewicz  7 , Piotr Grabarczyk  3
Affiliations

Human Intramuscular Hyperimmune Gamma Globulin (hIHGG) Anti-SARS-CoV-2-Characteristics of Intermediates and Final Product

Elzbieta Lachert et al. Viruses. .

Abstract

This study aims to characterize the intermediates, and the final product (FP) obtained during the production of human intramuscular hyperimmune gamma globulin anti-SARS-CoV-2 (hIHGG anti-SARS-CoV-2) and to determine its stability. Material and methods: hIHGG anti-SARS-CoV-2 was fractionated from 270 convalescent plasma donations with the Cohn method. Prior to fractionation, the plasma was inactivated (Theraflex MB Plasma). Samples were defined using enzyme immunoassays (EIA) for anti-S1, anti-RBD S1, and anti-N antibodies, and neutralization assays with SARS-CoV-2 (VN) and pseudoviruses (PVN, decorated with SARS-CoV-2 S protein). Results were expressed as a titer (EIA) or 50% of the neutralization titer (IC50) estimated in a four-parameter nonlinear regression model. Results: Concentration of anti-S1 antibodies in plasma was similar before and after inactivation. Following fractionation, the anti-S1, anti-RBD, and anti-N (total tests) titers in FP were concentrated approximately 15-fold from 1:4 to 1:63 (1800 BAU/mL), 7-fold from 1:111 to 1:802 and from 1:13 to 1:88, respectively. During production, the IgA (anti-S1) antibody titer was reduced to an undetectable level and the IgM (anti-RBD) titer from 1:115 to 1:24. The neutralizing antibodies (nAb) titer increased in both VN (from 1:40 to 1:160) and PVN (IC50 from 63 to 313). The concentration of specific IgG in the FP did not change significantly for 14 months. Conclusions: The hIHGG anti-SARS-CoV-2 was stable, with concentration up to approximately 15-fold nAb compared to the source plasma pool.

Keywords: COVID-19; SARS-CoV-2; convalescent plasma; gamma globulin; human intramuscular hyperimmune gamma globulin anti-SARS-CoV-2 (hIHGG anti-SARS-CoV-2).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
hIHGG anti-SARS-CoV-2 production.
Figure 2
Figure 2
Histogram of anti-SARS-CoV-2 antibodies reactivity in EIA assays in convalescent plasma units used for the production of hIHGG anti-SARS-CoV-2: (a) Wantai anti-S1 RBD Ab Total—IgM, IgA and IgG (n = 270, S/Co < 1 negative result, S/Co > 19.9 over result); (b) iFlash anti-S1 IgG (n = 206, <10 AU/mL—negative); (c) Euroimmun anti-S1 IgG (n = 265, S/Co < 0.8 negative, 0.8–1.1 gray zone, >1.1 positive); (d) Euroimmun IgA (n = 177, S/Co < 0.8 negative, 0.8–1.1 gray zone, >1.1 positive). Above bars % of tested samples is presented.
Figure 2
Figure 2
Histogram of anti-SARS-CoV-2 antibodies reactivity in EIA assays in convalescent plasma units used for the production of hIHGG anti-SARS-CoV-2: (a) Wantai anti-S1 RBD Ab Total—IgM, IgA and IgG (n = 270, S/Co < 1 negative result, S/Co > 19.9 over result); (b) iFlash anti-S1 IgG (n = 206, <10 AU/mL—negative); (c) Euroimmun anti-S1 IgG (n = 265, S/Co < 0.8 negative, 0.8–1.1 gray zone, >1.1 positive); (d) Euroimmun IgA (n = 177, S/Co < 0.8 negative, 0.8–1.1 gray zone, >1.1 positive). Above bars % of tested samples is presented.
Figure 3
Figure 3
Comparison of iFlash test reactivity (anti-S1 SARS-CoV-2 IgG antibody assay) in 206 CP donations before and after inactivation—no statistically significant differences in the pairwise Wilcoxon test were observed, p = 0.502.
See this image and copyright information in PMC

References

    1. Tea F., Ospina Stella A., Aggarwal A., Ross Darley D., Pilli D., Vitale D., Merheb V., Lee F.X., Cunningham P., Walker G.J., et al. SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants. PLoS Med. 2021;18:e1003656. doi: 10.1371/journal.pmed.1003656. - DOI - PMC - PubMed
    1. Valdez-Cruz N.A., García-Hernández E., Espitia C., Cobos-Marín L., Altamirano C., Bando-Campos C.G., Cofas-Vargas L.F., Coronado-Aceves E.W., González-Hernández R.A., Hernández-Peralta P., et al. Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment. Microb. Cell Factories. 2021;20:88. doi: 10.1186/s12934-021-01576-5. - DOI - PMC - PubMed
    1. Wooding D.J., Bach H. Treatment of COVID-19 with convalescent plasma: Lessons from past coronavirus outbreaks. Clin. Microbiol. Infect. 2020;26:1436–1446. doi: 10.1016/j.cmi.2020.08.005. - DOI - PMC - PubMed
    1. Tworek A., Jaroń K., Uszyńska-Kałuża B., Rydzewski A., Gil R., Deptała A., Franek E., Wójtowicz R., Życińska K., Walecka I., et al. Convalescent plasma treatment is associated with lower mortality and better outcomes in high-risk COVID-19 patients—Propensity-score matched case-control study. Int. J. Infect. Dis. 2021;105:209–215. doi: 10.1016/j.ijid.2021.02.054. - DOI - PMC - PubMed
    1. Rojas M., Anaya J.-M. Why will it never be known if convalescent plasma is effective for COVID-19. J. Transl Autoimmun. 2020;3:100069. doi: 10.1016/j.jtauto.2020.100069. - DOI - PMC - PubMed

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