Immunogenicity and safety of rapid scheme vaccination against tick-borne encephalitis in HIV-1 infected persons

Abstract Tick-borne encephalitis (TBE) is a vector-borne infection associated with a variety of potentially serious complications and sequelae. Vaccination against TBE is strongly recommended for people living in endemic areas. There are two TBE vaccination schemes – standard and rapid – which differ in the onset of protection. With vaccination in a rapid schedule, protection starts as early as 4 weeks after the first dose and is therefore especially recommended for non-immune individuals travelling to endemic areas. Both schemes work reliably in immunocompetent individuals, but only little is known about how TBE vaccination works in people with HIV infection. Our aim was to assess the immunogenicity and safety of the rapid scheme of TBE vaccination in HIV-1 infected individuals. Concentrations of TBE-specific IgG > 126 VIEU/ml were considered protective. The seroprotection rate was 35.7% on day 28 and 39.3% on day 60. There were no differences between responders and non-responders in baseline and nadir CD4 + T lymphocytes. No serious adverse events were observed after vaccination. The immunogenicity of the TBE vaccination was unsatisfactory in our study and early protection was only achieved in a small proportion of vaccinees. Therefore, TBE vaccination with the rapid scheme cannot be recommended for HIV-1 infected individuals.

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Feasibility of onchocerciasis elimination using a “test-and-not-treat” strategy in Loa loa co-endemic areas

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1829 ◽

2020 ◽

Author(s):

David J Blok ◽

Joseph Kamgno ◽

Sebastien D Pion ◽

Hugues C Nana-Djeunga ◽

Yannick Niamsi-Emalio ◽

...

Keyword(s):

Adverse Events ◽

Drug Administration ◽

Mass Drug Administration ◽

Treatment Duration ◽

Loa Loa ◽

Serious Adverse Events ◽

Endemic Areas ◽

The Individual ◽

The Impact ◽

Main Strategy

Abstract Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe but associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L. loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated pre-control mf prevalence levels from 2-40%. The impact of TaNT was simulated under varying levels of participation, systematic non-participation and exclusion from ivermectin due to high L. loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30-40% pre-control mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic non-participation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than six months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L. loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.

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Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

Nature Medicine ◽

10.1038/s41591-021-01509-0 ◽

2021 ◽

Author(s):

Kathryn E. Stephenson ◽

Boris Julg ◽

C. Sabrina Tan ◽

Rebecca Zash ◽

Stephen R. Walsh ◽

...

Keyword(s):

Viral Load ◽

T Cell ◽

Adverse Events ◽

Antiviral Activity ◽

Controlled Trial ◽

Phase 1 ◽

Serious Adverse Events ◽

Double Blind ◽

Cell Counts ◽

Hiv 1

AbstractHuman immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

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Antiretroviral agents: Focus on Maraviroc for the Treatment of HIV-1-Infected Adults

Clinical Medicine Insights Therapeutics ◽

10.4137/cmt.s5420 ◽

2010 ◽

Vol 2 ◽

pp. CMT.S5420

Author(s):

SL. Pett ◽

S. Emery ◽

AD. Kelleher ◽

DA. Cooper

Keyword(s):

Hiv Infection ◽

Chemokine Receptors ◽

Hiv Transmission ◽

Hiv Therapy ◽

Ccr5 Receptor ◽

Tick Borne Encephalitis ◽

Hiv Entry ◽

Orally Bioavailable ◽

Hiv Envelope ◽

Hiv 1

Over a decade has passed since several groups identified the chemokine receptors CXCR4 and CCR5 as key co-receptors for HIV entry. CCR5 is more important in HIV transmission and during the early course of HIV infection. It is also apparent that protection from HIV infection is afforded to those lacking CCR5–-the so called delta-32 homozygotes; in those heterozygous for this mutation, an attenuated course of HIV-infection is observed. Provocatively, those with modified expression of CCR5 are physiologically normal with the exception of poorer outcomes with some of the viral encephalitides specifically West Nile virus and Tick Borne encephalitis. The small molecule, orally-bioavailable CCR5 receptor antagonists, including, maraviroc (MVC), are allosteric inhibitors that lock the CCR5 receptor into a conformation such that the receptor is not able to bind HIV envelope protein; the molecules also variably block intracellular signalling induced by different receptor-binding chemokines. The aims of this review on the CCR5 receptor inhibitors are to summarise information relevant to treatment in individuals with HIV-1 infection. Data from the licensing studies, the side-effect profile and putative long-term risks of CCR5 receptor inhibitor exposure, tropism testing and mechanisms of resistance will be reviewed. The potential for using this class of agent as an immunomodulating agent will be detailed. Given that MVC is the only licensed drug in this class at present and reflecting the greater body of work describing this agent, the majority of information in this review relates to MVC. Last, the authors propose the place of MVC in the hierarchy of HIV therapy and future opportunities for research.

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Phase I Safety and Immunogenicity Evaluations of an Alphavirus Replicon HIV-1 Subtype CgagVaccine in Healthy HIV-1-Uninfected Adults

Clinical and Vaccine Immunology ◽

10.1128/cvi.00258-12 ◽

2012 ◽

Vol 19 (10) ◽

pp. 1651-1660 ◽

Cited By ~ 32

Author(s):

M. Wecker ◽

P. Gilbert ◽

N. Russell ◽

J. Hural ◽

M. Allen ◽

...

Keyword(s):

Adverse Events ◽

Cytotoxic T Lymphocyte ◽

Intracellular Cytokine Staining ◽

The United States ◽

Enzyme Linked Immunosorbent Assay ◽

Subtype C ◽

Serious Adverse Events ◽

Double Blind ◽

Preclinical Data ◽

Hiv 1

ABSTRACTOn the basis of positive preclinical data, we evaluated the safety and immunogenicity of an alphavirus replicon HIV-1 subtype Cgagvaccine (AVX101), expressing a nonmyristoylated form of Gag, in two double-blind, randomized, placebo-controlled clinical trials in healthy HIV-1-uninfected adults. Escalating doses of AVX101 or placebo were administered subcutaneously to participants in the United States and Southern Africa. Because of vaccine stability issues, the first trial was halted prior to completion of all dose levels and a second trial was implemented. The second trial was also stopped prematurely due to documentation issues with the contract manufacturer. Safety and immunogenicity were evaluated through assessments of reactogenicity, reports of adverse events, and assessment of replication-competent and Venezuelan equine encephalitis (VEE) viremia. Immunogenicity was measured using the following assays: enzyme-linked immunosorbent assay (ELISA), chromium 51 (51Cr)-release cytotoxic T lymphocyte (CTL), gamma interferon (IFN-γ) ELISpot, intracellular cytokine staining (ICS), and lymphoproliferation assay (LPA). Anti-vector antibodies were also measured. AVX101 was well tolerated and exhibited only modest local reactogenicity. There were 5 serious adverse events reported during the trials; none were considered related to the study vaccine. In contrast to the preclinical data, immune responses in humans were limited. Only low levels of binding antibodies and T-cell responses were seen at the highest doses. This trial also highlighted the difficulties in developing a novel vector for HIV.

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TBE in Croatia

Tick-borne encephalitis - The Book ◽

10.33442/26613980_12b7-3 ◽

2020 ◽

Keyword(s):

Tick Species ◽

Limited Data ◽

Notifiable Disease ◽

Genetic Characteristics ◽

Central European ◽

Tick Borne Encephalitis ◽

Tbe Virus ◽

Endemic Areas ◽

European Subtype

Even though tick-borne encephalitis (TBE) has been a notifiable disease in Croatia since 2007, there are no or only limited data available on the occurring tick species in the endemic areas, on the prevalence of TBE virus (TBEV) in ticks, its distribution in Croatia, and its genetic characteristics. Reporting of human cases also is very scarce. The Central European subtype of virus (TBEV-EU) appears to be present in Croatia

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Statin-induced adverse effects – facts and genes

Orvosi Hetilap ◽

10.1556/oh.2013.29530 ◽

2013 ◽

Vol 154 (3) ◽

pp. 83-92

Author(s):

Mariann Harangi ◽

Noémi Zsíros ◽

Lilla Juhász ◽

György Paragh

Keyword(s):

Risk Factors ◽

Single Nucleotide Polymorphisms ◽

Adverse Effects ◽

Adverse Events ◽

Statin Therapy ◽

Significant Proportion ◽

Gene Mutations ◽

Nucleotide Polymorphisms ◽

Serious Adverse Events ◽

Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

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Phosphene perceptions and safety of chronic visual cortex stimulation in a blind subject

Journal of Neurosurgery ◽

10.3171/2019.3.jns182774 ◽

2020 ◽

Vol 132 (6) ◽

pp. 2000-2007 ◽

Cited By ~ 3

Author(s):

Soroush Niketeghad ◽

Abirami Muralidharan ◽

Uday Patel ◽

Jessy D. Dorn ◽

Laura Bonelli ◽

...

Keyword(s):

Visual Cortex ◽

Adverse Events ◽

Clinical Intervention ◽

Occipital Cortex ◽

Neuronal Population ◽

Serious Adverse Events ◽

Stimulation Parameters ◽

The Right ◽

Visual Cortical ◽

Stimulation Of

Stimulation of primary visual cortices has the potential to restore some degree of vision to blind individuals. Developing safe and reliable visual cortical prostheses requires assessment of the long-term stability, feasibility, and safety of generating stimulation-evoked perceptions.A NeuroPace responsive neurostimulation system was implanted in a blind individual with an 8-year history of bare light perception, and stimulation-evoked phosphenes were evaluated over 19 months (41 test sessions). Electrical stimulation was delivered via two four-contact subdural electrode strips implanted over the right medial occipital cortex. Current and charge thresholds for eliciting visual perception (phosphenes) were measured, as were the shape, size, location, and intensity of the phosphenes. Adverse events were also assessed.Stimulation of all contacts resulted in phosphene perception. Phosphenes appeared completely or partially in the left hemifield. Stimulation of the electrodes below the calcarine sulcus elicited phosphenes in the superior hemifield and vice versa. Changing the stimulation parameters of frequency, pulse width, and burst duration affected current thresholds for eliciting phosphenes, and increasing the amplitude or frequency of stimulation resulted in brighter perceptions. While stimulation thresholds decreased between an average of 5% and 12% after 19 months, spatial mapping of phosphenes remained consistent over time. Although no serious adverse events were observed, the subject experienced mild headaches and dizziness in three instances, symptoms that did not persist for more than a few hours and for which no clinical intervention was required.Using an off-the-shelf neurostimulator, the authors were able to reliably generate phosphenes in different areas of the visual field over 19 months with no serious adverse events, providing preliminary proof of feasibility and safety to proceed with visual epicortical prosthetic clinical trials. Moreover, they systematically explored the relationship between stimulation parameters and phosphene thresholds and discovered the direct relation of perception thresholds based on primary visual cortex (V1) neuronal population excitation thresholds.

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