Viral Proteins under 70 Kilodaltons in Size Prevent the Development of Long-Lasting B-Cell Immune Memory and IgG2a Prevention in COVID-19 Vaccines.

Coronavirus disease 2019 (COVID-19) consists of a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. But there exist other infectious respiratory syndromes that have the same initial respiratory symptoms, show similar pattern in the size of the antigenic proteins and release comparable cytokines pathways, but with an unlike response magnitude. Here we propose that COVID-19 disease wrong response in the host immune system can be explained in the perspective of the antigen viral size. In COVID-19 sepsis, the < 70 kDa antigens activate the B-cell receptor (BCR), which modulates the shift in the pattern of T-helper 1 (Th1) to Th2 cytokines, increases the release of interleukin-10 (IL-10) and the up-regulation of the membrane form of tumor necrosis factor alpha (TNF-α), promoting the production of immunoglobulin G1 (IgG1)- and IgG3-neutralizing antibodies, but failing in IgG2a production and in developing long-lasting B-cell immune memory. The sustained infected cells lysis overfeeds high levels of viral proteins < 70 kDa, increases B-cell activation and, in the shift from a Th1 to a Th2 immune response, can trigger a cytokine storm. The continuous BCR activation increases IL-10 release that can lead to cytokine storm, apoptosis, and immune paralysis. Here, we propose a new vaccine design using the polymerization of viral antigens that could be ready in short time, would be cheap and easy to develop because it is based on classic technologies available in every country, is safe because it does not employ genetic material, and would able to promote long-lasting B-cell immune memory and IgG2a production.

Multicentre physiological reference intervals for serum concentrations of immunoglobulins A, G and M, complement C3c and C4 measured with Tina-Quant reagents systems.

BACKGROUND: Clinical laboratories seeking accreditation for compliance with ISO 15189:2003 need to demonstrate that the physiological reference intervals communicated to all users of the laboratory service are appropriate for the patient population served and for the measurement systems used. In the case of immunological quantities, few articles have been published in peer-reviewed journals. METHODS: A total of 21 clinical laboratories in different regions of Spain collaborated in identifying reference individuals and determining adult reference intervals for some immunological quantities measured using RD/Hitachi Modular Analytics analysers and Tina-Quant reagent systems. These immunological quantities are the mass concentrations of immunoglobulin A, immunoglobulin G, immunoglobulin M, complement C3c and complement C4 in serum. All the logistic work was carried out in co-operation with the supplier of the reagents and analysers (Roche Diagnostics España, S.L., Sant Cugat del Vallès, Catalonia, Spain). From the set of reference values obtained by each laboratory, multicentre reference limits were estimated non-parametrically. RESULTS AND CONCLUSIONS: The reference intervals estimated in this study for concentrations of serum components under consideration are: complement C3c, 0.62-1.64 g/L for women and men; complement C4, 0.14-0.72 g/L for women and men; immunoglobulin A, 0.89-4.80 g/L for women and men; immunoglobulin G, 6.5-14.3 g/L for women and men; and immunoglobulin M, 0.48-3.38 g/L for women and 0.41-2.46 g/L for men.