Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys.

The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine. PAPERCLIP:

Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome.

Pathogenic simian immunodeficiency virus (SIV) infection is associated with enteropathy, which likely contributes to AIDS progression. To identify candidate etiologies for AIDS enteropathy, we used next-generation sequencing to define the enteric virome during SIV infection in nonhuman primates. Pathogenic, but not nonpathogenic, SIV infection was associated with significant expansion of the enteric virome. We identified at least 32 previously undescribed enteric viruses during pathogenic SIV infection and confirmed their presence by using viral culture and PCR testing. We detected unsuspected mucosal adenovirus infection associated with enteritis as well as parvovirus viremia in animals with advanced AIDS, indicating the pathogenic potential of SIV-associated expansion of the enteric virome. No association between pathogenic SIV infection and the family-level taxonomy of enteric bacteria was detected. Thus, enteric viral infections may contribute to AIDS enteropathy and disease progression. These findings underline the importance of metagenomic analysis of the virome for understanding AIDS pathogenesis.

Adenovirus serotype 26 and 35 vectors induce simian immunodeficiency virus-specific T lymphocyte responses in foreskin in rhesus monkeys.

UNLABELLED: Foreskin is the principal site of heterosexual HIV-1 infection in men. However, little is known about HIV-1-specific immune responses or inflammation in foreskin. To the best of our knowledge, no previous studies have assessed immune responses to candidate HIV-1 vaccines in foreskin. Using the rhesus monkey model, we show that intramuscular immunization with adenovirus serotype 26 and 35 vectors expressing SIV antigens elicited durable SIV Gag-specific CD4(+) and CD8(+) T cell responses in foreskin that were detectable for more than 1 year following vaccination. Gag-specific CD4(+) and CD8(+) T cells were also detectable in foreskin of SIV- and SHIV-infected animals and were at least comparable in magnitude to those in peripheral blood. However, unlike peripheral blood T cells, the majority of foreskin T cells exhibited transitional memory or effector memory phenotype and expressed higher levels of the activation markers CD69, HLA-DR, and CCR5, although vaccination did not further enhance foreskin CD4(+) T cell activation. These findings suggest that systemic vaccination strategies can elicit potentially important SIV-specific cellular immunity in foreskin. Further characterization of vaccine-elicited immune responses and inflammation in foreskin is warranted. IMPORTANCE: We demonstrate here the induction of SIV-specific cellular immune responses in foreskin by adenovirus serotype 26 and 35 vaccine vectors. Foreskin T cells were more activated than peripheral blood T cells, but foreskin T cells were not further activated by vaccination. These findings suggest that alternative serotype adenovirus vectors induce potentially important immune responses in foreskin.

Immune dysregulation, polyendocrinopathy and enteropathy, X-linked (IPEX) syndrome due to a mutation in FOXP3, modified by a pathogenic variant in SON (SON DNA-binding protein).

Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked, known as IPEX syndrome, is a rare heterogeneous condition. Zhu-Tokita-Takenouchi-Kim Syndrome (ZTTK) is an autosomal dominant condition arising from a mutation in the SON gene, which is involved in mRNA splicing. A case showing interactions of mutations in these two genes is described in which both conditions become non-typical.

An unusual presentation of neonatal rhabdomyosarcoma: a case report.

A full-term infant with an unremarkable prenatal course presented at birth with a large midline facial mass and smaller masses in the head and neck. In addition, multiple diffuse flesh-colored nodules spread along all the upper and lower limbs. An extensive evaluation to cover a broad differential diagnosis of infectious, lymphatic/vascular, and oncologic etiology was undertaken. The initial suspicion was confirmed by biopsy of the skin lesion as congenital alveolar rhabdomyosarcoma (RMS). RMS is the most common soft tissue sarcoma that occurs in childhood. However, neonatal RMS is exceedingly rare. The infant's initial treatment included vincristine, dactinomycin, and cyclophosphamide in addition to salvage ifosfamide and etoposide, which were dose-adjusted for age. Herein, we present a case of an infant with RMS who showed initial improvement before relapsing and succumbing to her disease at 5 months of age. A review of the limited literature available on this rare condition and newer treatment regimens with improved mortality rates is performed.

Hepatitis C genotype 1 mosaic vaccines are immunogenic in mice and induce stronger T-cell responses than natural strains.

Despite improved hepatitis C virus (HCV) treatments, vaccines remain an effective and economic option for curtailing the epidemic. Mosaic protein HCV genotype 1 vaccine candidates designed to address HCV diversity were immunogenic in mice. They elicited stronger T-cell responses to NS3-NS4a and E1-E2 proteins than did natural strains, as assessed with vaccine-matched peptides.