Immunogenicity and Safety of a Third COVID-19 BNT162b2 mRNA Vaccine Dose in 5- to 11-Year Olds

In this ongoing study, substantially increased ancestral SARSCoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5 to 11-year olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability profile was acceptable.Peer reviewe

Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies.

PURPOSE: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. METHODS: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable. RESULTS: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca2+-binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4. CONCLUSION: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans

A Case of Invasive Gastrointestinal Mycotypha Infection in a Patient with Neutropenia

Gastrointestinal mucormycosis is a rare life-threatening infection to which neutropenic patients are especially vulnerable. Mycotypha microspora is a mucormycete that has not been described as a human pathogen. We discuss the successful eradication of gastrointestinal Mycotypha microspora in a neutropenic patient with simultaneous pulmonary Aspergillus fumigatus infection

Exophiala (Wangiella) dermatitidis Prosthetic Aortic Valve Endocarditis and Prosthetic Graft Infection in an Immune Competent Patient

Exophiala (Wangiella) dermatitidis is an emerging dematiaceous fungus associated with high mortality rates and is a rare cause of endocarditis. We describe the first case of E. dermatitidis endocarditis of a prosthetic aortic valve and aortic graft in an immune competent patient with no clear risk factors of hematological acquisition

Rapidly growing Mycobacterium infections after cosmetic surgery in medical tourists: the Bronx experience and a review of the literature

Background: Medical tourism is increasingly popular for elective cosmetic surgical procedures. However, medical tourism has been accompanied by reports of post-surgical infections due to rapidly growing mycobacteria (RGM). The authors’ experience working with patients with RGM infections who have returned to the USA after traveling abroad for cosmetic surgical procedures is described here. Methods: Patients who developed RGM infections after undergoing cosmetic surgeries abroad and who presented at the Montefiore Medical Center (Bronx, New York, USA) between August 2015 and June 2016 were identified. A review of patient medical records was performed. Results: Four patients who presented with culture-proven RGM infections at the sites of recent cosmetic procedures were identified. All patients were treated with a combination of antibiotics and aggressive surgical treatment. Conclusions: This case series of RGM infections following recent cosmetic surgeries abroad highlights the risks of medical tourism. Close monitoring of affected patients by surgical and infectious disease specialties is necessary, as aggressive surgical debridement combined with appropriate antibiotic regimens is needed to achieve cure. Given the increasing reports of post-surgical RGM infections, consultants should have a low threshold for suspecting RGM, as rapid diagnosis may accelerate the initiation of targeted treatment and minimize morbidity

Homologous boosting with adenoviral serotype 5 HIV vaccine (rAd5) vector can boost antibody responses despite preexisting vector-specific immunity in a randomized phase I clinical trial.

Needle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine.Thirty-one adults, 18-55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 1010 PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks.Overall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boost.Biojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.Clinicaltrials.gov NCT00709605 NCT00709605

Group 1 Env-specific antibody responses stratified by pre-existing reciprocal 90% Ad5 neutralization titers.

<p>Antibody responses were measured using ELISA against HIV-1 envelope proteins matching vaccine antigen. Data from 4 weeks post rAd5 vaccine is shown as individual data points and box plots showing the median, 25^th and 75^th quartiles for group 1 stratified by reciprocal dilution 90% Ad5 neutralization titer. A comparison of Biojector and N/S mode of delivery is shown. Red represents the responders and blue represents the non-responders. Anti-EnvA binding antibody levels are plotted as log 10 of ELISA titer, and are shown as representative of responses to EnvB and EnvC.</p

Local reactogenicity following rAd5 vaccine.

<p>All subjects who received rAd5 vaccination by needle injection (n = 15) or by Biojector injection (n = 16) were counted once at worst severity over 5 days for solicited local parameters. The graph shows the percentage with mild or moderate reaction; there were no severe reactions. The results for local parameters of pain, swelling and redness are shown individually, while “Any Local” represents the worst severity for any of the local parameters. There were no statistically significant differences between the needle and Biojector reactogenicity except for “Any Local”.</p

Total CD4 and CD8 T-cell responses (IFN-γ, IL-2 and TNF-α) to all vaccine antigens (Gag, Pol and Env) were not significantly (p = >0.05) improved by Biojector in secondary immunization.

<p>This graph represents total CD4 and CD8 T cell responses to all vaccine antigens Env, Gag and Pol for each study sub group. Total percentage of cytokine responses on log scale is shown on the y-axis. The combined T cell responses are shown over a longitudinal period at 4, 24 and 76 and 128 weeks following rAd5 vaccine on the x-axis. Responses are shown for the Biojector and needle groups for both primary and secondary immunization.</p

Schematic diagram of study design and vaccination schedule.

<p>The CONSORT diagram indicates the number of subjects screened to complete enrollment of 31 subjects. Subjects were stratified as group 1 (primary immunization) versus group 2 (secondary immunization) and randomized to receive rAd5 vaccine by Biojector or needle and syringe. Group 1 included 8 subjects with adenovirus serotype 5 neutralizing antibody reciprocal titer ≤500 randomized equally into sub groups 1a and 1b.</p