Working Together to Find a Voice: Recommendations for Voice Healthcare Based on Expert-By-Experience and Practitioner Consensus.

OBJECTIVES: Voice care services aim to provide effective and meaningful voice care. Current practice guidance recommends a multidisciplinary voice care approach, supported by the evidence-base and practitioner experience. However, unlike other areas of physical and mental health, current voice care guidance does not explicitly include the voices of experts-by-experience, meaning those who have lived experience of voice difficulties. The perspectives of those working within nonclinical voice professions, such as vocal coaches, are also often omitted. There is therefore a need for updated practice guidance which prioritizes expert-by-experience and nonclinical perspectives. METHODS: Vocal Health Education hosted a consensus meeting in London, UK. The meeting was coproduced with experts-by-experience, and attendees included those with lived experience of voice difficulties and practitioners across a range of disciplines within voice care. The content of the meeting was synthesized into themes and associated recommendations were drafted and agreed to by all attendees. RESULTS: The consensus statement offers practical advice to those working in voice care. Recommendations are offered for multidisciplinary and biopsychosocial voice care, with a focus on person-centered practice and the valuing of lived experience. Through discussion, consensus was reached regarding recommendations for voice care assessment and treatment, practitioner approach, psychosocial considerations, and service design. The need for greater expert-by-experience involvement, coproduction, and co-construction was emphasized throughout. CONCLUSIONS: This report emphasizes the voices of those with lived experience. It highlights ways of updating or improving current care, with the aim of informing clinical practice as well as research and service development. The consensus statement is the first in voice care to include experts-by-experience at the center of its recommendations, underlining the need for more coproduced and co-constructed research and practice within voice healthcare.

High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses.

We have developed a high-throughput platform to detect the presence of HIV-1 and SIV-specific ADCC-mediating antibody responses. The assay is based on the hydrolysis of a cell-permeable fluorogenic peptide substrate containing a sequence recognized by the serine protease, Granzyme B (GzB). GzB is delivered into target cells by cytotoxic effector cells as a result of antigen (Ag)-specific Ab-Fcγ receptor interactions. Within the target cells, effector cell-derived GzB hydrolyzes the substrate, generating a fluorescent signal that allows individual target cells that have received a lethal hit to be identified by flow cytometry. Results are reported as the percentage of target cells with GzB activity (%GzB). Freshly isolated or cryopreserved PBMC and/or NK cells can be used as effector cells. CEM.NKR cells expressing the CCR5 co-receptor are used as a target cells following: (i) coating with recombinant envelope glycoprotein, (ii) infection with infectious molecular clones expressing the Env antigens of primary and lab adapted viruses, or (iii) chronic infection with a variant of HIV-1/IIIB, termed A1953. In addition, primary CD4(+) T cells infected with HIV-1 in vitro can also be used as targets. The assay is highly reproducible with a coefficient of variation of less than 25%. Target and effector cell populations, in the absence of serum/plasma, were used to calculate background (8.6 ± 2.3%). We determined that an initial dilution of 1:50 and 1:100 is required for testing of human and non-human primate samples, respectively. This assay allows for rapid quantification of HIV-1 or SIV-specific ADCC-mediating antibodies that develop in response to vaccination, or in the natural course of infection, thus providing researchers with a new methodology for investigating the role of ADCC-mediating antibodies as correlates of control or prevention of HIV-1 and SIV infection.

Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge.

The current study assessed the immunogenicity and protective efficacy of various prime-boost vaccine regimens in rhesus macaques using combinations of recombinant DNA (rDNA), recombinant MVA (rMVA), and subunit gp140 protein. The rDNA and rMVA vectors were constructed to express Env from HIV-1 subtype CRF01_AE and Gag-Pol from CRF01_AE or SIVmac 239. One of the rMVAs, MVA/CMDR, has been recently tested in humans. Immunizations were administered at months 0 and 1 (prime) and months 3 and 6 (boost). After priming, HIV env-specific serum IgG was detected in monkeys receiving gp140 alone or rMVA but not in those receiving rDNA. Titers were enhanced in these groups after boosting either with gp140 alone or with rMVA plus gp140. The groups that received the rDNA prime developed env-specific IgG after boosting with rMVA with or without gp140. HIV Env-specific serum IgG binding antibodies were elicited more frequently and of higher titer, and breadth of neutralizing antibodies was increased with the inclusion of the subunit Env boost. T cell responses were measured by tetramer binding to Gag p11c in Mamu-A*01 macaques, and by IFN-γ ELISPOT assay to SIV-Gag. T cell responses were induced after vaccination with the highest responses seen in macaques immunized with rDNA and rMVA. Macaques were challenged intravenously with a novel SHIV-E virus (SIVmac239 Gag-Pol with an HIV-1 subtype E-Env CAR402). Post challenge with SHIV-E, antibody titers were boosted in all groups and peaked at 4 weeks. Robust T cell responses were seen in all groups post challenge and in macaques immunized with rDNA and rMVA a clear boosting of responses was seen. A greater than two-log drop in RNA copies/ml at peak viremia and earlier set point was achieved in macaques primed with rDNA, and boosted with rMVA/SHIV-AE plus gp140. Post challenge viremia in macaques immunized with other regimens was not significantly different to that of controls. These results demonstrate that a gp140 subunit and inclusion of SIV Gag-Pol may be critical for control of SHIV post challenge.