https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)00239-1.pdf

Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial.

https://spiral.imperial.ac.uk/bitstream/10044/1/56396/5/1-s2.0-S1525001617305944-main.pdf

Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses

Oral pre-exposure prophylaxis (PrEP) can reduce HIV incidence among at-risk persons. However, for PrEP to have an impact in decreasing HIV incidence, clinicians will need to be willing to prescribe PrEP. HIV specialists are experienced in using antiretroviral medications, and could readily provide PrEP, but may not care for HIV-uninfected patients. Six focus groups with 39 Boston area HIV care providers were conducted (May-June 2012) to assess perceived barriers and facilitators to prescribing PrEP. Participants articulated logistical and theoretical barriers, such as concerns about PrEP effectiveness in real-world settings, potential unintended consequences (e.g., risk disinhibition and medication toxicity), and a belief that PrEP provision would be more feasible in primary care clinics. They identified several facilitators to prescribing PrEP, including patient motivation and normative guidelines. Overall, participants reported limited prescribing intentions. Without interventions to address HIV providers' concerns, implementation of PrEP in HIV clinics may be limited.

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HIV Providers’ Perceived Barriers and Facilitators to Implementing Pre-exposure Prophylaxis in Care Settings: A Qualitative Study

Albert Liu and colleagues report early experiences with uptake and delivery of pre-exposure prophylaxis(PrEP)for HIV prevention in three different settings in San Francisco. PrEP can be an important component of a comprehensive HIV prevention program and can complement efforts to increase HIV testing, linkage to care, and early initiation of antiretroviral therapy. Please see later in the article for the Editors' Summary

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Early Experiences Implementing Pre-exposure Prophylaxis (PrEP) for HIV Prevention in San Francisco

BackgroundAlthough Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain–Barre syndrome are well described. There are no approved vaccines against ZIKV infection. MethodsIn this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. ResultsThe median age of the participants was 38 years, and 60% were women; 78% were white, and 22% black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., in...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1708120

Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report.

DNA-based immunization offers several advantages [1]. DNA vaccines contain nonliving, nonreplicating, and nontransmissible material, providing an improved safety profile over live attenuated viral vectors. They do not elicit antivector immunity, retaining potency through multiple boost cycles. In theory, DNA vaccines are simple and relatively inexpensive to construct, readily produced in large quantities, easy to characterize, and stable and can be combined into complex formulations.

Despite the early enthusiasm from results of studies in small animals, DNA vaccines have not generated robust immune responses in humans [2–6]. The amount of antigen produced by each transfected cell is low because of the low transcription rate of antigen sequences being driven off the cytomegalovirus promoter [7–9]. One approach to augment the immunogenicity of DNA is to combine the DNA vaccine with a plasmid cytokine adjuvant [10–13]. Interleukin 12 (IL-12) is a key cytokine for the induction of cellular immune responses [14, 15]. Interleukin 15 (IL-15) is a member of the common cytokine receptor γ-chain family [16–18] that fosters development of long-lived memory T-cell responses [19–21].

A newer strategy for increasing immune potency has been to deliver the plasmids with in vivo electroporation. Electroporation enhances uptake of DNA into cells by temporarily generating an electrical field that increases the permeability of cell membranes and moves the macromolecules through the briefly open membrane pores. Clinical applications of electroporation have been tested, especially in cancer treatment and gene therapy [22–24]. Electroporation has elicited HIV-specific cellular immune responses in mice [25] and simian immunodeficiency virus–specific immune responses in macaques [26]. In macaque studies, genetic optimization, electroporation, and IL-12 plasmid adjuvant have improved the immunogenicity of DNA vaccines in vivo [26]. More recently, Vasan et al reported on a trial that showed the potential to increase vaccine-induced cellular responses to a DNA vaccine relative to intramuscular injection alone [27]. However, electroporation remains investigational [28] and has not been licensed by the Food and Drug Administration for clinical use. This is the first report on the combination of these approaches in humans. Here, we summarize the results of 2 trials of an HIV plasmid DNA vaccine, PENNVAX®-B (PV), one investigating HIV consensus clade B Gag, Pol, and Env with IL-12 or IL-15 plasmid cytokine adjuvants delivered by intramuscular injection without electroporation (HIV Vaccine Trials Network [HVTN] study 070) and the other investigating the same vaccine with plasmid IL-12 delivered intramuscularly with electroporation (HVTN study 080). The results illustrate the power of these combined DNA approaches to generate impressive immune responses in humans.

/pdf/safety-and-comparative-immunogenicity-of-an-hiv-1-dna-2ziqssyvs0.pdf

Safety and Comparative Immunogenicity of an HIV-1 DNA Vaccine in Combination with Plasmid Interleukin 12 and Impact of Intramuscular Electroporation for Delivery

Tecovirimat and the Treatment of Monkeypox - Past, Present, and Future Considerations.

In November 2010, the iPrEx study reported that pre-exposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine reduced HIV infections by 44% among men who have sex with men and subsequent trials corroborated efficacy among heterosexual men and women. During regularly scheduled follow-up visits from January-March 2011, participants in an ongoing phase 2b vaccine efficacy trial completed an anonymous web survey about PrEP. Among 376 respondents, 17% reported they were very likely to use PrEP in the next year. Non-white participants were more likely to use PrEP. Among those with some level of interest, intent to use PrEP was greatest if the drug were available through the clinical trial or health insurance. Most (91%) believed taking PrEP would not change their willingness to stay in the vaccine trial and few thought it would affect recruitment. As key stakeholders, currently enrolled trial participants can offer vital input about emerging prevention technologies that may affect the design of future HIV vaccine and non-vaccine prevention trials.

/pdf/intentions-to-use-preexposure-prophylaxis-among-current-1a7gydnn3h.pdf

Adam Sherwat

Papers

Safety and Comparative Immunogenicity of an HIV-1 DNA Vaccine in Combination with Plasmid Interleukin 12 and Impact of Intramuscular Electroporation for Delivery

Tecovirimat and the Treatment of Monkeypox - Past, Present, and Future Considerations.

Intentions to use preexposure prophylaxis among current phase 2B preventive HIV-1 vaccine efficacy trial participants.