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Vaccination in HIV

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https://www.readbyqxmd.com/read/28103319/an-hsv-2-trivalent-vaccine-is-immunogenic-in-rhesus-macaques-and-highly-efficacious-in-guinea-pigs
#1
Sita Awasthi, Lauren M Hook, Carolyn E Shaw, Bapi Pahar, Jacob A Stagray, David Liu, Ronald S Veazey, Harvey M Friedman
A genital herpes vaccine is urgently needed to prevent pain and suffering, reduce the incidence of neonatal herpes, and decrease the risk of HIV acquisition and transmission that accompanies genital infection. We evaluated a trivalent HSV-2 subunit antigen vaccine administered with CpG and alum in rhesus macaques and guinea pigs. The vaccine contains glycoproteins C, D and E (gC2, gD2, gE2) to block virus entry by gD2 and immune evasion by gC2 and gE2. In rhesus macaques, the trivalent vaccine induced plasma and mucosa neutralizing antibodies, antibodies that block gC2 and gE2 immune evasion activities, and stimulated CD4 T cell responses...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28102671/structural-analysis-of-glycosylated-intact-hiv-1-gp120-b12-antibody-complex-using-hydroxyl-radical-protein-footprinting
#2
Xiaoyan Li, Oliver C Grant, Keigo Ito, Aaron Wallace, Shixia Wang, Peng Zhao, Lance Wells, Shan Lu, Robert J Woods, Joshua S Sharp
Glycoprotein gp120 is a surface antigen and virulence factor of the human immunodeficiency virus-1 (HIV-1). Broadly neutralizing antibodies (bNAbs) that are reactive to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system due to its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28100618/influence-of-the-envelope-gp120-phe-43-cavity-on-hiv-1-sensitivity-to-adcc-responses
#3
Jérémie Prévost, Daria Zoubchenok, Jonathan Richard, Maxime Veillette, Beatriz Pacheco, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Kiat Ruxrungtham, Torsak Bunupuradah, Sodsai Tovanabutra, Kwan-Ki Hwang, M Anthony Moody, Barton F Haynes, Mattia Bonsignori, Joseph Sodroski, Daniel E Kaufmann, George M Shaw, Agnès L Chenine, Andrés Finzi
: HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to CD4-bound state...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28099188/hepatitis-b-incidence-and-prevention-with-antiretroviral-therapy-among-hiv-positive-individuals-in-rakai-uganda
#4
Emmanuel Seremba, Victor Ssempijja, Sarah Kalibbala, Ronald H Gray, Maria J Wawer, Fred Nalugoda, Corey Casper, Warren T Phipps, Ponsiano Ocama, David Serwadda, David L Thomas, Steven Reynolds
OBJECTIVE: Antiretroviral therapy (ART) may interfere with replication of hepatitis B (HBV) raising the hypothesis that HBV infection might be prevented by ART. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda. METHODS: We screened stored sera from 944 HIV-infected adults enrolled in the Rakai Community Cohort Study between September 2003 and March 2015 for evidence of HBV exposure. Serum from participants who tested anti-HBc negative (497) at baseline were tested over 3-7 consecutive survey rounds for incident HBV...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28097434/work-related-infections-in-dentistry-risk-perception-and-preventive-measures
#5
Tatjana Ramich, Peter Eickholz, Sabine Wicker
OBJECTIVES: Evaluation of (1) the risk perception of work-related infections in dentistry, (2) the vaccination status, (3) knowledge of the blood-borne pathogens and HIV post-exposure prophylaxis (PEP) as well as (4) use of personal protective equipment (PPE) (gloves, goggles, mask) among the staff and students of the Center of Dentistry and Oral Medicine (ZZMK [Carolinum]) of the Goethe University Frankfurt/Main. MATERIAL AND METHODS: All staff (dentists, dental assistants) and students of the ZZMK with direct contact to patients were asked to anonymously complete a questionnaire...
January 18, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28095712/current-views-on-the-potential-for-development-of-a-hiv-vaccine
#6
Kristen W Cohen, Nicole Frahm
Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials. Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses...
January 18, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28093536/noma-overview-of-a-neglected-disease-and-human-rights-violation
#7
REVIEW
M Leila Srour, Klaas Marck, Denise Baratti-Mayer
Noma is an orofacial gangrene affecting malnourished children and mainly observed in tropical countries, particularly sub-Saharan Africa. Epidemiological data on noma are scarce, but a current estimate of the global incidence is 30,000-40,000 cases per year, with a mortality rate of approximately 85% and a burden of disease calculated to be a loss of 1-10 million disability-adjusted life years. The etiology of noma is multifactorial with malnutrition as an ever present factor, often in combination with concomitant diseases, such as measles, malaria, and human immunodeficiency virus (HIV), and poor oral hygiene...
January 16, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28089302/germinal-center-lymphocyte-ratios-and-successful-hiv-vaccines
#8
Paula Gonzalez-Figueroa, Jonathan A Roco, Carola G Vinuesa
Current HIV vaccines are poor inducers of neutralizing antibodies (nAbs). A recent study in Cell Reports used serial fine-needle aspirates from rhesus macaque lymph nodes following HIV-1 surface envelope glycoprotein (Env) trimer immunization, generating a substantial production of HIV-1 nAbs. A remarkable correlation was found between antibody titers and a high frequency and ratio of germinal center B and T follicular helper (TFH) lymphocytes.
January 11, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28080988/medical-mycology-and-fungal-immunology-new-research-perspectives-addressing-a-major-world-health-challenge
#9
REVIEW
Neil A R Gow, Mihai G Netea
Fungi cause more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies and more than a million deaths each year. Global mortality owing to fungal infections is greater than for malaria and breast cancer and is equivalent to that owing to tuberculosis (TB) and HIV. These statistics evidence fungal infections as a major threat to human health and a major burden to healthcare budgets worldwide. Those patients who are at greatest risk of life-threatening fungal infections include those who have weakened immunity or have suffered trauma or other predisposing infections such as HIV...
December 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28079828/vaccination-with-10-valent-pneumococcal-conjugate-vaccine-in-infants-according-to-hiv-status
#10
Shabir A Madhi, Anthonet Koen, Lisa Jose, Nadia van Niekerk, Peter V Adrian, Clare Cutland, Nancy François, Javier Ruiz-Guiñazú, Juan-Pablo Yarzabal, Marta Moreira, Dorota Borys, Lode Schuerman
BACKGROUND: Phase III, open-label, single-center, controlled study in South Africa (ClinicalTrials.gov: NCT00829010) to evaluate immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) children. METHODS: Children stratified by HIV status received PHiD-CV primary vaccination (age 6/10/14 weeks; coadministered with routine childhood vaccines) and booster dose (age 9-10 months)...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28077659/hiv-controllers-exhibit-enhanced-frequencies-of-mhc-class-ii-tetramer-gag-specific-cd4-t-cells-in-chronic-clade-c-hiv-1-infection
#11
Faatima Laher, Srinika Ranasinghe, Filippos Porichis, Nikoshia Mewalal, Karyn Pretorius, Nasreen Ismail, Søren Buus, Anette Stryhn, Mary Carrington, Bruce D Walker, Thumbi Ndung'u, Zaza M Ndhlovu
: Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, understanding the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection remains incomplete. Recently, MHC class II tetramers have emerged as a powerful tool for interrogating antigen specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C infected persons...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077588/first-in-human-evaluation-of-the-safety-and-immunogenicity-of-an-intranasally-administered-replication-competent-sendai-virus-vectored-hiv-type-1-gag-vaccine-induction-of-potent-t-cell-or-antibody-responses-in-prime-boost-regimens
#12
Julien Nyombayire, Omu Anzala, Brian Gazzard, Etienne Karita, Philip Bergin, Peter Hayes, Jakub Kopycinski, Gloria Omosa-Manyonyi, Akil Jackson, Jean Bizimana, Bashir Farah, Eddy Sayeed, Christopher L Parks, Makoto Inoue, Takashi Hironaka, Hiroto Hara, Tsugumine Shu, Tetsuro Matano, Len Dally, Burc Barin, Harriet Park, Jill Gilmour, Angela Lombardo, Jean-Louis Excler, Patricia Fast, Dagna S Laufer, Josephine H Cox
BACKGROUND:  We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. METHODS:  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH)...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28077023/hiv-associated-sub-acute-sclerosing-panencephalitis-an-emerging-threat
#13
Abi Manesh, Mahesh Moorthy, Rini Bandopadhyay, Priscilla Rupali
Earlier age of measles virus infection predisposes to development of sub-acute sclerosing panencephalitis (SSPE) and this risk is heightened in HIV-infected children. We describe a HIV-infected young adult on antiretroviral therapy, presenting with a non-classical, fulminant form of SSPE to highlight the unpredictable nature of measles presentation. The recent spate of measles outbreaks due to virus introduction in populations with sub-optimal vaccine coverage or waning immunity and co-existing paediatric HIV cohorts is a cause for concern...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28076415/structure-and-recognition-of-a-novel-hiv-1-gp120-gp41-interface-antibody-that-caused-mper-exposure-through-viral-escape
#14
Constantinos Kurt Wibmer, Jason Gorman, Gabriel Ozorowski, Jinal N Bhiman, Daniel J Sheward, Debra H Elliott, Julie Rouelle, Ashley Smira, M Gordon Joyce, Nonkululeko Ndabambi, Aliaksandr Druz, Mangai Asokan, Dennis R Burton, Mark Connors, Salim S Abdool Karim, John R Mascola, James E Robinson, Andrew B Ward, Carolyn Williamson, Peter D Kwong, Lynn Morris, Penny L Moore
A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28073435/evaluation-of-the-efficacy-of-a-therapeutic-hiv-vaccine-by-in-vitro-stimulation-assay
#15
Xiaozhou He, Wandi Wang, Ke Xu, Xia Feng, Yi Zeng
A novel method for HIV vaccine efficacy evaluation was established and the experimental conditions optimized. This novel method was then applied to determine whether a recombinant adenovirus type 5 HIV therapeutic vaccine expressing Gag antigen (Ad5-HIVgag) could stimulate HIV-specific cellular responses in vitro. The results indicated that HIV-specific IFN-gama production lymphocytes were induced by the Ad5-HIVgag vaccine. Compared with other methods, this in vitro stimulation method is safe and time-efficient, and the result is more intuitive...
January 4, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28073289/generation-and-characterization-of-hiv-1-transmitted-and-founder-virus-consensus-sequence-from-intravenous-drug-users-in-xinjiang-china
#16
Fan Li, Liying Ma, Yi Feng, Jing Hu, Na Ni, Yuhua Ruan, Yiming Shao
HIV-1 transmission in intravenous drug users (IDUs) have been characterized by high genetic multiplicity, suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full length gp160 gene obtained by single genome sequencing(SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence(IDU.CON). All the T/F virus was classified as subtype CRF07_BC, and predicted to be CCR5-tropic virus...
January 10, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28070215/multiple-hpv-infections-in-female-sex-workers-in-western-kenya-implications-for-prophylactic-vaccines-within-this-sub-population
#17
Sonia Menon, Davy van den Broeck, Rodolfo Rossi, Emilomo Ogbe, Hillary Mabeya
BACKGROUND: Whilst the imputed role of High Risk (HR) HPV infection in the development of cervical lesions and cancer has been established, the high number of HPV genotypes that Female Sex workers (FSW) harbour warrants that the synergistic effects of potential HR (pHR) and HR HPV genotypes be elucidated to assess the potential impact of prophylactic vaccines. This population in Kenya also harbours a number of other vaginal infections and STIs, including bacterial vaginosis (BV), trichomonas vaginalis (TV) and candida spp...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28069884/purification-of-zika-virus-rna-dependent-rna-polymerase-and-its-use-to-identify-small-molecule-zika-inhibitors
#18
Hong-Tao Xu, Said A Hassounah, Susan P Colby-Germinario, Maureen Oliveira, Clare Fogarty, Yudong Quan, Yingshan Han, Olga Golubkov, Ilinca Ibanescu, Bluma Brenner, Brent R Stranix, Mark A Wainberg
BACKGROUND: The viral RNA-dependent RNA polymerase (RdRp) enzymes of the Flaviviridae family are essential for viral replication and are logically important targets for development of antiviral therapeutic agents. Zika virus (ZIKV) is a rapidly re-emerging human pathogen for which no vaccine or antiviral agent is currently available. METHODS: To facilitate development of ZIKV RdRp inhibitors, we have established an RdRp assay using purified recombinant ZIKV NS5 polymerase...
January 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28069361/dna-mva-protein-vaccination-of-rhesus-macaques-induces-hiv-specific-immunity-in-mucosal-associated-lymph-nodes-and-functional-antibodies
#19
Gerald K Chege, Wendy A Burgers, Tracey L Müller, Clive M Gray, Enid G Shephard, Susan W Barnett, Guido Ferrari, David Montefiori, Carolyn Williamson, Anna-Lise Williamson
Successful future HIV vaccines are expected to generate an effective cellular and humoral response against the virus in both the peripheral blood and mucosal compartments. We previously reported the development of DNA-C and MVA-C vaccines based on HIV-1 subtype C and demonstrated their immunogenicity when given in a DNA prime-MVA boost combination in a nonhuman primate model. In the current study, rhesus macaques previously vaccinated with a DNA-C and MVA-C vaccine regimen were re-vaccinated 3.5years later with MVA-C followed by a protein vaccine based on HIV-1 subtype C envelope formulated with MF59 adjuvant (gp140Env/MF59), and finally a concurrent boost with both vaccines...
January 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28060797/t-memory-stem-cells-in-health-and-disease
#20
REVIEW
Luca Gattinoni, Daniel E Speiser, Mathias Lichterfeld, Chiara Bonini
T memory stem (TSCM) cells are a rare subset of memory lymphocytes endowed with the stem cell-like ability to self-renew and the multipotent capacity to reconstitute the entire spectrum of memory and effector T cell subsets. Cumulative evidence in mice, nonhuman primates and humans indicates that TSCM cells are minimally differentiated cells at the apex of the hierarchical system of memory T lymphocytes. Here we describe emerging findings demonstrating that TSCM cells, owing to their extreme longevity and robust potential for immune reconstitution, are central players in many physiological and pathological human processes...
January 6, 2017: Nature Medicine
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