Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity

H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H53) was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H53 antigen was a robust immunogen. Immunizing mice with H53 encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4+ T cell recall responses in mice. Finally, the H53-based polyanhydride nanovaccine induced protective immunity against a low-pathogenic H5N1 viral challenge. Informatics analyses indicated that mice receiving the nanovaccine formulations and subsequently challenged with virus were similar to naïve mice that were not challenged. The current studies provide a basis to further exploit the advantages of polyanhydride nanovaccines in pandemic scenarios

Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity.

H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H5₃) was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H5₃ antigen was a robust immunogen. Immunizing mice with H5₃ encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4(+) T cell recall responses in mice. Finally, the H5₃-based polyanhydride nanovaccine induced protective immunity against a low-pathogenic H5N1 viral challenge. Informatics analyses indicated that mice receiving the nanovaccine formulations and subsequently challenged with virus were similar to naïve mice that were not challenged. The current studies provide a basis to further exploit the advantages of polyanhydride nanovaccines in pandemic scenarios

Characterization of programmed -1 ribosomal frameshift signals in the interleukin 2 receptor gamma mRNA

Programmed -1 ribosomal frameshift (-1 PRF) signals are predicted to be present in ~10% of eukaryotic mRNA, suggesting a conserved role for -1 PRF in eukaryotic mRNA translation. This work focuses on -1 PRF in the interleukin 2 receptor gamma (IL2RG) mRNA. IL2RG is a component of receptors for six cytokines responsible for lymphocyte proliferation and differentiation. Altered expression of IL2RG is linked to immunodeficiency and lymphoma. We verified that the IL2RG mRNA has one potential -1 PRF signal in exon 3 that stimulates -1 frameshifting and a second in exon 8 that is definitively a -1 PRF signal. Both of these signals redirect the ribosome to a premature termination codon, suggesting -1 PRF alters IL2RG expression via NMD. Testing the effect of cancer patient associated mutations discovered in the exon 8 -1 PRF signal may elucidate a role for IL2RG -1 PRF in normal physiology and pathological phenotypes

Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity

H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H53) was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H53 antigen was a robust immunogen. Immunizing mice with H53 encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4+ T cell recall responses in mice. Finally, the H53-based polyanhydride nanovaccine induced protective immunity against a low-pathogenic H5N1 viral challenge. Informatics analyses indicated that mice receiving the nanovaccine formulations and subsequently challenged with virus were similar to naïve mice that were not challenged. The current studies provide a basis to further exploit the advantages of polyanhydride nanovaccines in pandemic scenarios.This article is from International Journal of Nanomedicine 10 (2015): 229, doi: 10.2147/IJN.S72264. Posted with permission.</p

Stereotactic radiosurgery for chordoma: a report from the North American Gamma Knife Consortium

BACKGROUND: Although considered slow-growing, low-grade malignancies, chordomas are locally aggressive and destructive tumors with high recurrence rates. OBJECTIVE: To assess patient survival, tumor control, complications, and selected variables that predict outcome in patients who underwent Gamma Knife stereotactic radiosurgery (SRS) as primary, adjuvant, or salvage management for chordomas of the skull base. METHODS: Six participating centers of the North American Gamma Knife Consortium identified 71 patients who underwent SRS for chordoma. The median patient age was 45 years (range, 7-80 years). The median SRS target volume was 7.1 cm³ (range, 0.9-109 cm³), and median margin dose was 15.0 Gy (range, 9-25 Gy). RESULTS: At a median follow-up of 5 years (range, 0.6-14 years) after SRS, 23 patients died of tumor progression. The 5-year actuarial overall survival after SRS was 80% for the entire group, 93% for the no prior fractionated radiation therapy (RT) group (n = 50), and 43% for the prior RT group (n = 21). Younger age, longer interval between initial diagnosis and SRS, no prior RT, \u3c 2 cranial nerve deficits, and smaller total tumor volume were significantly associated with longer patient survival. The 5-year treated tumor control rate after SRS was 66% for the entire group, 69% for the no prior RT group, and 62% for the prior RT group. Older age, recurrent group, prior RT, and larger tumor volume were significantly associated with worse tumor control. CONCLUSION: Stereotactic radiosurgery is a potent treatment option for small sized chordomas, especially in younger patients and as part of a multipronged attack that includes surgical resection when possible