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Background: Shigella species, which cause acute diarrheal disease, are transmitted via fecal-oral and sexual contact. To better understand the overlapping populations affected by Shigella infections and sexually transmitted infections (STIs) in the United States, we examined the occurrence of reported STIs within 24 months among shigellosis case-patients., Methods: Culture-confirmed Shigella cases diagnosed from 2007 to 2016 among residents of 6 US jurisdictions were matched to reports of STIs (chlamydia, gonorrhea, and all stages of syphilis) diagnosed 12 months before or after the shigellosis case. We examined epidemiologic characteristics and reported temporal trends of Shigella cases by sex and species., Results: From 2007 to 2016, 10,430 shigellosis cases were reported. The annual number of reported shigellosis cases across jurisdictions increased 70%, from 821 cases in 2007 to 1398 cases in 2016; males saw a larger increase compared with females. Twenty percent of male shigellosis case-patients had an STI reported in the reference period versus 4% of female case-patients. The percentage of male shigellosis case-patients with an STI increased from 11% (2007) to 28% (2016); the overall percentage among females remained low., Conclusions: We highlight the substantial proportion of males with shigellosis who were diagnosed with STIs within 24 months and the benefit of matching data across programs. Sexually transmitted infection screening may be warranted for male shigellosis case-patients., Competing Interests: Conflict of Interest and Sources of Funding: All authors have no conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Vaccination and passive antibody therapies are critical for controlling infectious diseases. Passive antibody administration has limitations, including the necessity for purification and multiple injections for efficacy. Vaccination is associated with a lag phase before generation of immunity. Novel approaches reported here utilize the benefits of both methods for the rapid generation of effective immunity., Methods: A novel antibody-based prophylaxis/therapy entailing the electroporation-mediated delivery of synthetic DNA plasmids encoding biologically active anti-chikungunya virus (CHIKV) envelope monoclonal antibody (dMAb) was designed and evaluated for antiviral efficacy, as well as for the ability to overcome shortcomings inherent with conventional active vaccination and passive immunotherapy., Results: One intramuscular injection of dMAb produced antibodies in vivo more rapidly than active vaccination with an anti-CHIKV DNA vaccine. This dMAb neutralized diverse CHIKV clinical isolates and protected mice from viral challenge. Combination of dMAb and the CHIKV DNA vaccine afforded rapid and long-lived protection., Conclusions: A DNA-based dMAb strategy induced rapid protection against an emerging viral infection. This method can be combined with DNA vaccination as a novel strategy to provide both short- and long-term protection against this emerging infectious disease. These studies have implications for pathogen treatment and control strategies., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen., (Copyright © 2015, American Association for the Advancement of Science.)

Melanoma is the most deadly type of skin cancer, constituting annually ∼ 75% of all cutaneous cancer-related deaths due to metastatic spread. Currently, because of metastatic spread, there are no effective treatment options for late-stage metastatic melanoma patients. Studies over the past two decades have provided insight into several complex molecular mechanisms as to how these malignancies evade immunological control, indicating the importance of immune escape or suppression for tumor survival. Thus, it is essential to develop innovative cancer strategies and address immune obstacles with the goal of generating more effective immunotherapies. One important area of study is to further elucidate the role and significance of myeloid-derived suppressor cells (MDSCs) in the maintenance of the tumor microenvironment. These cells possess a remarkable ability to suppress immune responses and, as such, facilitate tumor growth. Thus, MDSCs represent an important new target for preventing tumor progression and escape from immune control. In this study, we investigated the role of MDSCs in immune suppression of T cells in an antigen-specific B16 melanoma murine system utilizing a novel synthetic tyrosinase (Tyr) DNA vaccine therapy in both prophylactic and therapeutic models. This Tyr vaccine induced a robust and broad immune response, including directing CD8 T-cell infiltration into tumor sites. The vaccine also reduced the number of MDSCs in the tumor microenvironment through the downregulation of monocyte chemoattractant protein 1, interleukin-10, CXCL5 and arginase II, factors important for MDSC expansion. This novel synthetic DNA vaccine significantly reduced the melanoma tumor burden and increased survival in vivo, due likely, in part, to the facilitation of a change in the tumor microenvironment through MDSC suppression.

Background and Objectives: Non-ablative fractional lasers cause little down-time, however, some patients want more noticeable results with fewer treatments. The 1940 nm wavelength matches one of the water absorption peaks in the mid infrared band of electromagnetic energy. The skin absorption is much stronger than other non-ablative wavelengths (1410-1550 nm) and weaker than ablative wavelengths (Er:YAG or CO2). The objective of this study was to characterize clinical efficacy using this technology to treat photodamaged skin in human subjects., Materials and Methods: Under an IRB approved study, eleven subjects with facial photodamage (1 male and 10 female) were enrolled and completed the study. The fractional 1940 nm laser was comprised of a thulium rod pumped by a pulsed alexandrite laser. The fractional patterns were generated by four separate handpieces (two dot (0.48mm and 0.76mm dot-to-dot distance or pitch) and two grid geometries) whereby a larger beam was broken up into smaller microbeams by a microlens system or reflective square grids. The low -pitch circular dot array handpiece, which is used most frequently, has a macro-spot size of 12 mm and a total applied energy of approximately 2-5 J (~ 4-10 mJ per beamlet). Contact skin cooling (5-20degC) was provided via a sapphire window at the distal end of handpiece. Pulses from the dot handpieces were applied with 20% overlap. The microspot size for the dot handpieces was ~ 0.2-0.3 mm. The two grid pattern handpieces included 0.4 mm wide lines with 45% and 0.7 mm wide lines with 65% coverage. Each subject received 3 full-face treatments 4-6 weeks apart. Anesthesia was achieved by 5% lidocaine cream and a cold air chiller. Typical treatments were carried out with two passes. Outcome assessments included changes in pigment, rhytides, laxity, elastosis, and texture, using a diffuse pigmentation scale and the Alexiades-Armenakas Comprehensive Grading Scale of Rhytides, Laxity, and Photodamage. Photographs of each patient from prior to treatment, and 3 months after treatment were analyzed by 3 blinded physician raters. A paired t-test was applied for each category comparing the pre treatment and 3-month post treatment results., Results: Three months after the final treatment, (a) mean pigment improvement was 21.1%, (b) rhytides were reduced by 14.3%, (c) laxity was reduced by 8.9%, elastosis was reduced by 22.3%, and (e) texture scores were unchanged. Reductions in pigmentation, rhytides, and elastosis were statistically significant (P≤ 0.05). Clinical downtime was 3-5 days. Pain was variable (mean of 2.8/10) and side effects included two cases of mild focal vesiculation. No long-term side effects were noted. Histological analysis showed focal damage that extended about 200 μm deep to the surface., Conclusion: The 1940nm thulium laser is safe, well tolerated, and results in reduced downtime compared to traditional resurfacing. The study demonstrated that the 1940 nm thulium laser could achieve injury patterns capable of skin rejuvenation.

DNA vaccine-induced immunity can be enhanced by the co-delivery of synthetic gene-encoding molecular adjuvants. Many of these adjuvants have included cytokines, chemokines or co-stimulatory molecules that have been demonstrated to enhance vaccine-induced immunity by increasing the magnitude or type of immune responses and/or protective efficacy. In this way, through the use of adjuvants, immune responses can be highly customizable and functionally tailored for optimal efficacy against pathogen specific (i.e., infectious agent) or non-pathogen (i.e., cancer) antigens. In the novel study presented here, we examined the use of cellular transcription factors as molecular adjuvants. Specifically the co-delivery of (a) RelA, a subunit of the NF-κB transcription complex or (b) T-bet, a Th1-specific T box transcription factor, along with a prototypical DNA vaccine expressing HIV-1 proteins was evaluated. As well, all of the vaccines and adjuvants were administered to mice using in vivo electroporation (EP), a technology demonstrated to dramatically increase plasmid DNA transfection and subsequent transgene expression with concomitant enhancement of vaccine induced immune responses. As such, this study demonstrated that co-delivery of either adjuvant resulted in enhanced T and B cell responses, specifically characterized by increased T cell numbers, IFN-γ production, as well as enhanced antibody responses. This study demonstrates the use of cellular transcription factors as adjuvants for enhancing DNA vaccine-induced immunity.

An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs), and the elicitation of antibody-dependent cellular cytotoxicity (ADCC). Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP). However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.

Monoclonal antibody preparations have demonstrated considerable clinical utility in the treatment of specific malignancies, as well as inflammatory and infectious diseases. Antibodies are conventionally delivered by passive administration, typically requiring costly large-scale laboratory development and production. Additional limitations include the necessity for repeat administrations, and the length of in vivo potency. Therefore, the development of methods to generate therapeutic antibodies and antibody like molecules in vivo, distinct from an active antigen-based immunization strategy, would have considerable clinical utility. In fact, adeno-associated viral (AAV) vector mediated delivery of immunoglobulin genes with subsequent generation of functional antibodies has recently been developed. As well, anon-viral vector mediated nucleic acid based delivery technology could permit the generation of therapeutic/prophylactic antibodies in vivo, obviating potential safety issues associated with viral vector based gene delivery. This delivery strategy has limitations as well, mainly due to very low in vivo production and expression of protein from the delivered gene. In the study reported here we have constructed an "enhanced and optimized" DNA plasmid technology to generate immunoglobulin heavy and light chains (i.e., Fab fragments) from an established neutralizing anti-HIV envelope glycoprotein monoclonal antibody (VRC01). This "enhanced" DNA (E-DNA) plasmid technology includes codon/RNA optimization, leader sequence utilization, as well as targeted potentiation of delivery and expression of the Fab immunoglobulin genes through use of "adaptive" in vivo electroporation. The results demonstrate that delivery by this method of a single administration of the optimized Fab expressing constructs resulted in generation of Fab molecules in mouse sera possessing high antigen specific binding and HIV neutralization activity for at least 7 d after injection, against diverse HIV isolates. Importantly, this delivery strategy resulted in a rapid increase (i.e., in as little as 48 h) in Fab levels when compared with protein-based immunization. The active generation of functional Fab molecules in vivo has important conceptual and practical advantages over conventional ex vivo generation, purification and passive delivery of biologically active antibodies. Further study of this technique for the rapid generation and delivery of immunoglobulin and immunoglobulin like molecules is highly relevant and timely.

Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIKV-envelope DNA vaccine (pEnv) and the role of the CHIKV nonstructural gene 2 (nsP2) as an adjuvant for the induction of protective immune responses in a relevant mouse challenge model. When injected with the CHIKV pEnv alone, 70% of the immunized mice survived CHIKV challenge, whereas when co-injected with pEnv+pnsP2, 90% of the mice survived viral challenge. Mice also exhibited a delayed onset signs of illness, and a marked decrease in morbidity, suggesting a nsP2 mediated adjuvant effect. Co-injection of the pnsP2 adjuvant with pEnv also qualitatively and quantitatively increased antigen specific neutralizing antibody responses compared to vaccination with pEnv alone. In sum, these novel data imply that the addition of nsP2 to the pEnv vaccine enhances anti-CHIKV-Env immune responses and maybe useful to include in future CHIKV clinical vaccination strategies.

In diagnosing actinic prurigo (AP), the patients' ethnic background is very helpful as this condition is associated with very specific ethnic groups. We discuss a patient with an unknown family history who presented with a rash that initially seemed like lupus, but was subsequently diagnosed as AP upon further evaluations.