Xpert was easy to perform and displayed similar diagnostic accuracy as culture methods in children with suspected tuberculosis. Rapid turnaround times should reduce treatment delay and improve patient outcome, although sensitivity remains suboptimal and access is dependent on local laboratory infrastructure.

Background Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multi-clade DNA vaccine prime with a replication-defective Adenovirus type 5 (rAd5) boost. Methods The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B and C and subtype B gag, pol and nef, and a rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 1010 (n=24) or 1011 particle units (n=24), or DNA at 0, 1 and 2 months followed by rAd5 at either 1010 (n=114) or 1011 particle units (n=24) boosting at 6 months. Participants were followed for 24 weeks after the final immunization. Results The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Pre-existing Ad5 neutralizing antibody titer did not impact the frequency and magnitude of T cell responses in prime-boost recipients, but did impact the response rates in participants receiving rAd5 alone (p=0.037). Conclusion The DNA/rAd5 immunization regimen was safe and induced HIV-1 multi-clade T cell responses, which were not significantly affected by pre-existing rAd5 neutralizing antibody titer.

There is an urgent need for vaccines to counter the COVID-19 pandemic due to infections with severe acute respiratory syndrome coronavirus (SARS-CoV-2). Evidence from convalescent sera and preclinical studies has identified the viral Spike (S) protein as a key antigenic target for protective immune responses. We have applied an mRNA-based technology platform, RNActive®, to develop CVnCoV which contains sequence optimized mRNA coding for a stabilized form of S protein encapsulated in lipid nanoparticles (LNP). Following demonstration of protective immune responses against SARS-CoV-2 in animal models we performed a dose-escalation phase 1 study in healthy 18-60 year-old volunteers.This interim analysis shows that two doses of CVnCoV ranging from 2 μg to 12 μg per dose, administered 28 days apart were safe. No vaccine-related serious adverse events were reported. There were dose-dependent increases in frequency and severity of solicited systemic adverse events, and to a lesser extent of local reactions, but the majority were mild or moderate and transient in duration. Immune responses when measured as IgG antibodies against S protein or its receptor-binding domain (RBD) by ELISA, and SARS-CoV-2-virus neutralizing antibodies measured by micro-neutralization, displayed dose-dependent increases. Median titers measured in these assays two weeks after the second 12 μg dose were comparable to the median titers observed in convalescent sera from COVID-19 patients. Seroconversion (defined as a 4-fold increase over baseline titer) of virus neutralizing antibodies two weeks after the second vaccination occurred in all participants who received 12 μg doses.Preliminary results in the subset of subjects who were enrolled with known SARS-CoV-2 seropositivity at baseline show that CVnCoV is also safe and well tolerated in this population, and is able to boost the pre-existing immune response even at low dose levels.Based on these results, the 12 μg dose is selected for further clinical investigation, including a phase 2b/3 study that will investigate the efficacy, safety, and immunogenicity of the candidate vaccine CVnCoV.

Summary Background We used the RNActive® technology platform (CureVac N.V., Tübingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV‑2 spike (S) protein encapsulated in lipid nanoparticles (LNP). Methods This is an interim analysis of a dosage escalation phase 1 study in healthy 18–60-year-old volunteers in Hannover, Munich and Tübingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV‑2 S‑protein and receptor binding domain (RBD), and SARS-CoV‑2 neutralizing titers (MN50). Results In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S‑protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S‑protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 μg group. Responses to 12 μg were comparable to those observed in convalescent sera from known COVID-19 patients. Conclusion In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera.

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BackgroundIntradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools.MethodsIn this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids) compared to two “simplified” regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46.Results129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups.ConclusionsA simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA.Trial RegistrationWorld Health Organization International Clinical Trials Registry Platform PACTR2010050002122368

The lipodystrophy syndrome (LDS) is a growing problem in human immunodeficiency virus (HIV)-positive patients treated with highly active antiretroviral therapy (HAART). It is characterized by alterations of body composition and metabolic abnormalities. The goal of the study was to investigate attitudes toward health condition, well-being, and individual appearance in relation to LDS. Outpatients between July and October 2000 in an HIV-specialized unit at the University Hospital of Düsseldorf, Germany, underwent clinical evaluation and received a standardized written questionnaire. Of 389 patients eligible for analysis, 313 patients returned completed questionnaires (response rate, 80.5%). LDS was observed in 37.7%; the predominant manifestation was lipoatrophy of the face (32.9%). Individuals with and without LDS did not differ significantly in their attitude to the quality of their health condition and the amount of disturbance of their well-being by HIV infection. Participants with LDS felt recognizable as HIV-positive by physical appearance in 30.1%, compared to 18.3% in patients without LDS (p = 0.027). This difference became more pronounced after adjustment for gender, age, stage of disease, CD4 cell count, and duration of HAART (odds ratio, 2.04, 95%-confidence interval [CI] 1.09-3.84). In conclusion, LDS does not seem to disturb the general attitude toward health condition and well-being. However, patients presenting with lipodystrophy are about twice as likely to feel recognizable as HIV-positive by their physical appearance. LDS may thus be perceived as a characteristic mark of being HIV-positive by affected persons. A stigmatizing effect and social disadvantages may be the consequences.