Messenger RNA Vaccine Technology: Success for SARS-CoV-2 and Prospects for an HIV-1 Vaccine.

Over the past several years, messenger RNA (mRNA) vaccine has evolved from a term familiar only to vaccine scientists into one easily recognized by much of the general population. This change occurred because of the remarkable success of effective and safe mRNA vaccines during the COVID-19 pandemic that saved countless lives. Although mRNA vaccine technology has a clear use for combating future emerging diseases, its role in fighting currently known pathogens, such as HIV-1, is not well defined.

In situ analysis of neuronal injury and neuroinflammation during HIV-1 infection.

Background: Since the introduction of combination antiretroviral therapy (cART) the brain has become an important human immunodeficiency virus (HIV) reservoir due to the relatively low penetration of many drugs utilized in cART into the central nervous system (CNS). Given the inherent limitations of directly assessing acute HIV infection in the brains of people living with HIV (PLWH), animal models, such as humanized mouse models, offer the most effective means of studying the effects of different viral strains and their impact on HIV infection in the CNS. To evaluate CNS pathology during HIV-1 infection in the humanized bone marrow/liver/thymus (BLT) mouse model, a histological analysis was conducted on five CNS regions, including the frontal cortex, hippocampus, striatum, cerebellum, and spinal cord, to delineate the neuronal (MAP2ab, NeuN) and neuroinflammatory (GFAP, Iba-1) changes induced by two viral strains after 2 weeks and 8 weeks post-infection.

Impact of Chronic HIV Infection on Acute Immune Responses to SARS-CoV-2.

There is mounting evidence that HIV infection is a risk factor for severe presentations of COVID-19. We hypothesized that the persistent immune activation associated with chronic HIV infection contributes to worsened outcomes during acute COVID-19. The goals of this study were to provide an in-depth analysis of immune response to acute COVID-19 and investigate relationships between immune responses and clinical outcomes in an unvaccinated, sex- and race-matched cohort of people with HIV (PWH, n = 20) and people without HIV (PWOH, n = 41).

The role of immune activation and antigen persistence in acute and long COVID.

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global coronavirus disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited syndrome comparable to other upper respiratory viral pathogens, a portion of individuals develop severe illness leading to substantial morbidity and mortality. Furthermore, an estimated 10%-20% of SARS-CoV-2 infections are followed by post-acute sequelae of COVID-19 (PASC), or long COVID.

HLA-II-Associated HIV-1 Adaptation Decreases CD4 T-Cell Responses in HIV-1 Vaccine Recipients.

Epitopes with evidence of HLA-II-associated adaptation induce poorly immunogenic CD4 T-cell responses in HIV-positive (HIV) individuals. Many such escaped CD4 T-cell epitopes are encoded by HIV-1 vaccines being evaluated in clinical trials. Here, we assessed whether this viral adaptation adversely impacts CD4 T-cell responses following HIV-1 vaccination, thereby representing escaped epitopes.

SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence.

T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5+PD1+ CD4 T cells).

Duration of post-COVID-19 symptoms is associated with sustained SARS-CoV-2-specific immune responses.

A subset of COVID-19 patients exhibit post-acute sequelae of COVID-19 (PASC), but little is known about the immune signatures associated with these syndromes. We investigated longitudinal peripheral blood samples in 50 individuals with previously confirmed SARS-CoV-2 infection, including 20 who experienced prolonged duration of COVID-19 symptoms (lasting more than 30 days; median = 74 days) compared with 30 who had symptom resolution within 20 days. Individuals with prolonged symptom duration maintained antigen-specific T cell response magnitudes to SARS-CoV-2 spike protein in CD4+ and circulating T follicular helper cell populations during late convalescence, while those without persistent symptoms demonstrated an expected decline.

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection.

SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and nonhospitalized individuals.

SARS-CoV-2-specific peripheral T follicular helper cells correlate with neutralizing antibodies and increase during convalescence.

T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 21 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mount at least one CD4 T-cell response, and 48% of individuals mount detectable SARS-CoV-2-specific peripheral T follicular helper cells (pTfh, defined as CXCR5+PD1+ CD4 T cells).

Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL.

New therapies for Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) patients are urgently needed. The genetic landscape of Ph-like ALL is characterized by a diverse array of kinase-activating alterations (including rearrangements, sequence mutations, and copy number alterations), suggesting that patients with Ph-like ALL are candidates for targeted therapy, similar to BCR-ABL1 ALL. We sought to investigate the functional role and targetability of the spectrum of kinase-activating alterations identified in Ph-like ALL.

Photobleaching studies reveal that a single amino acid polymorphism is responsible for the differential binding affinities of linker histone subtypes H1.1 and H1.5.

Mammals express six major somatic linker histone subtypes, all of which display dynamic binding to chromatin, characterized by transient binding at a given location followed by rapid translocation to a new site. Using photobleaching techniques, we systematically measured the exchange rate of all six mouse H1 subtypes to determine their relative chromatin-binding affinity. Two subtypes, H1.