Highlights Platforms for COVID-19 vaccine development. Clinical Trials in COVID-19 and their results. Use of preformed antibodies. Vaccine development and its limitations.

No abstract

Correspondence between the T-cell epitope responses of vaccine immunogens and those of pathogen antigens is critical to vaccine efficacy. In the present study, we analyzed the spectrum of immune responses of mice to three different forms of the SARS coronavirus nucleocapsid (N): (1) exogenous recombinant protein (N-GST) with Freund's adjuvant; (2) DNA encoding unmodified N as an endogenous cytoplasmic protein (pN); and (3) DNA encoding N as a LAMP-1 chimera targeted to the lysosomal MHC II compartment (p-LAMP-N). Lysosomal trafficking of the LAMP/N chimera in transfected cells was documented by both confocal and immunoelectron microscopy. The responses of the immunized mice differed markedly. The strongest T-cell IFN-gamma and CTL responses were to the LAMP-N chimera followed by the pN immunogen. In contrast, N-GST elicited strong T cell IL-4 but minimal IFN-gamma responses and a much greater antibody response. Despite these differences, however, the immunodominant T-cell ELISpot responses to each of the three immunogens were elicited by the same N peptides, with the greatest responses being generated by a cluster of five overlapping peptides, N76-114, each of which contained nonameric H2d binding domains with high binding scores for both class I and, except for N76-93, class II alleles. These results demonstrate that processing and presentation of N, whether exogenously or endogenously derived, resulted in common immunodominant epitopes, supporting the usefulness of modified antigen delivery and trafficking forms and, in particular, LAMP chimeras as vaccine candidates. Nevertheless, the profiles of T-cell responses were distinctly different. The pronounced Th-2 and humoral response to N protein plus adjuvant are in contrast to the balanced IFN-gamma and IL-4 responses and strong memory CTL responses to the LAMP-N chimera.

No abstract

The effect of chronic aluminium exposure (25 mg/kg b.wt.) was studied on the lipid composition and various membrane-bound enzymes in different regions of monkey brain. Aluminium (Al) administration caused a significant decrease in the total lipid, glycolipid, and phospholipid content of primate brain. Cholesterol levels and the phospholipid to cholesterol ratio were, however, markedly increased as a consequence of Al administration, thereby indicating a loss of membrane integrity. This was further confirmed when Al treatment was found to have a significant effect on the various membrane-bound enzymes in terms of decreased activities of Na+ K+ ATPase and acetylcholinesterase, along with a decrease in the activity of the myelin-specific enzyme, 2' 3'-cyclic nucleotide phosphohydrolase.