Background: HIV p24 is an extracellular HIV antigen involved in viral replication. Falling p24 antibody responses are associated with clinical disease progression and their preservation with non-progressive disease. Stimulation of p24 antibody production by immunization to delay progression was the basis of discontinued p24 vaccine. We studied a therapy-naive HIV+ man from Sydney, Australia, infected in 1988. He received the HIV-p24-virus like particle (VLP) vaccine in 1993, and continues to show vigorous p24 antigen responses (>4% p24-specific CD4+ T cells), coupled with undetectable plasma viremia. We defined immune-protective correlates of p24 vaccination at the proteomic level through parallel retrospective analysis of cellular immune responses to p24 antigen in CD4+ and CD8+ T cells and CD14+ monocytes at viremic and aviremic phases using antibody-array. We found statistically significant coordinated up-regulation by all three cell-types with high fold-changes in fractalkine, ITAC, IGFBP-2, and MIP-1α in the aviremic phase. TECK and TRAIL-R4 were down-regulated in the viremic phase and up-regulated in the aviremic phase. The up-regulation of fractalkine in all three cell-types coincided with protective effect, whereas the dysfunction in anti-apoptotic chemokines with the loss of immune function. This study highlights the fact that induction of HIV-1-specific helper cells together with coordinated cellular immune response (p < 0.001) might be important in immunotherapeutic interventions and HIV vaccine development.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the human host can lead to various clinical manifestations, from symptomless carriers to mild to moderate to severe/critical illness. Therefore, the clinical classification of SARS-CoV-2 disease, based on severity, is a reliable way to predict disease states in SARS-CoV-2 infection. Recent studies on genomics, transcriptomics, epigenomics, and immunogenomics, along with spatial analysis of immune cells have delineated and defined the categorization of these disease groups using these high throughout technologies. These technologies hold the promise of providing not only a detailed but a holistic view of SARS-CoV-2-led pathogenesis. The main genomic, cellular, and immunologic features of each disease category, and what separates them spatially and molecularly are discussed in this brief review to provide a foundational spatial understanding of SARS-CoV-2 immunopathogenesis.
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