Challenges and Progress in Designing Broad-Spectrum Vaccines Against Rapidly Mutating Viruses.

Viruses evolve to evade prior immunity, causing significant disease burden. Vaccine effectiveness deteriorates as pathogens mutate, requiring redesign. This is a problem that has grown worse due to population increase, global travel, and farming practices.

Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR.

Recent advances in cancer immunotherapy have completely revolutionized cancer treatment strategies. Nonetheless, the increasing incidence of immune-related adverse events (irAEs) is now limiting the overall benefits of these treatments. irAEs are well-recognized side effects of some of the most effective cancer immunotherapy agents, including antibody blockade of the cytotoxic T-lymphocyte-associated protein 4 and programmed death protein 1/programmed-death ligand 1 pathways.

A monocentric phase I study of vemurafenib plus cobimetinib plus PEG-interferon (VEMUPLINT) in advanced melanoma patients harboring the V600BRAF mutation.

Background: Studies carried out in vitro and in a mouse model have shown that BRAF inhibitors enhance the effects of IFN-α on BRAFV600E melanoma cells through the inhibition of ERK. Therefore, the combination of vemurafenib and IFN-α in patients with BRAFV600E melanoma may provide therapeutic benefits; MEK inhibition may prevent the reactivation of the MAPK pathway induced by BRAF inhibitor resistance.

Patients And Methods: In a phase I study, adult patients with advanced BRAFV600-mutated melanoma were treated with vemurafenib + PEG-IFN-α-2b or vemurafenib + cobimetinib + PEG-IFN-α-2b, to assess the safety of the combination and the upregulation of IFN-α/β receptor-1 (IFNAR1).

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women.

Specific causes of preterm birth remain unclear. Several recent studies have suggested that immune changes during pregnancy are associated with the timing of delivery, yet few studies have been performed in low-income country settings where the rates of preterm birth are the highest. We conducted a retrospective nested case-control evaluation within a longitudinal study among HIV-uninfected pregnant Kenyan women.

Pregnancy-Induced Alterations in NK Cell Phenotype and Function.

Pregnant women are particularly susceptible to complications of influenza A virus infection, which may result from pregnancy-induced changes in the function of immune cells, including natural killer (NK) cells. To better understand NK cell function during pregnancy, we assessed the ability of the two main subsets of NK cells, CD56, and CD56 NK cells, to respond to influenza-virus infected cells and tumor cells. During pregnancy, CD56 and CD56 NK cells displayed enhanced functional responses to both infected and tumor cells, with increased expression of degranulation markers and elevated frequency of NK cells producing IFN-γ.

Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation.

Purpose: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent preclinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective antitumor T-cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in patients with malignant glioma.

Zika Virus Infection Induces Cranial Neural Crest Cells to Produce Cytokines at Levels Detrimental for Neurogenesis.

Zika virus (ZIKV) infection during pregnancy is linked to microcephaly, which is attributed to infection of developing brain structures. ZIKV infects neural progenitor cells in vitro, though its effects on other developmentally relevant stem cell populations, including cranial neural crest cells (CNCCs), have not been assessed. CNCCs give rise to most cranial bones and exert paracrine effects on the developing brain.

Increased Proinflammatory Responses of Monocytes and Plasmacytoid Dendritic Cells to Influenza A Virus Infection During Pregnancy.

Pregnancy-induced alterations in immunity may contribute to the increased morbidity associated with influenza A virus infection during pregnancy. We characterized the immune response of monocytes and plasmacytoid dendritic cells (pDCs) to influenza A virus infection in 21 pregnant and 21 nonpregnant women. In pregnant women, monocytes and pDCs exhibit an exaggerated proinflammatory immune response to 2 strains of influenza A virus, compared with nonpregnant women, characterized by increased expression of major histocompatibility complex class II (approximately 2.

Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells.

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections, and comprise nearly 8% of the human genome. The most recently acquired human ERV is HERVK(HML-2), which repeatedly infected the primate lineage both before and after the divergence of the human and chimpanzee common ancestor. Unlike most other human ERVs, HERVK retained multiple copies of intact open reading frames encoding retroviral proteins.

Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine.

Background: Inactivated influenza vaccine (IIV) is recommended during pregnancy to prevent influenza infection and its complications in pregnant women and their infants. However, the extent to which pregnancy modifies the antibody response to vaccination remains unclear, and prior studies have focused primarily on hemagglutinin inhibition (HI) titers. A more comprehensive understanding of how pregnancy modifies the humoral immune response to influenza vaccination will aid in maximizing vaccine efficacy.

Association between latent proviral characteristics and immune activation in antiretrovirus-treated human immunodeficiency virus type 1-infected adults.

Unlabelled: Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively treated with antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in driving HIV-associated immune activation.