The New York City Board of Health (NYCBH) vaccinia virus is the currently licensed vaccine for use in the US against smallpox. The vaccine under investigation in this study has been attenuated by deletion of the innate immune evasion gene, E3L, and shown to be protective in homologous virus mouse challenge and heterologous virus mouse and rabbit challenge models. In this study we compared NYCBH deleted for the E3L gene (NYCBHΔE3L) to NYCBH for the ability to induce phosphorylation of proinflammatory signaling proteins and the ability to protect cynomolgous macaques from heterologous challenge with monkeypox virus (MPXV). NYCBHΔE3L induced phosphorylation of PKR and eIF2α as well as p38, SAPK/JNK, and IRF3 which can lead to induction of proinflammatory gene transcription. Vaccination of macaques with two doses of NYCBHΔE3L resulted in negligible pock formation at the site of scarification in comparison to vaccination using a single dose of NYCBH, but still elicited neutralizing antibodies and protected 75% of the animals from mortality after challenge with MPXV. However, NYCBHΔE3L-vaccinated animals developed a high number of secondary skin lesions and blood viral load similar to that seen in unvaccinated controls. The NYCBHΔE3L-vaccinated animals that survived MPXV challenge were able to show resolution of blood viral load, a decrease in number of skin lesions, and an improved clinical score by three weeks post challenge. These results suggest that although the highly attenuated NYCBHΔE3L allows proinflammatory signal transduction to occur, it does not provide full protection against monkeypox challenge.

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Vaccinia virus deleted for the innate immune evasion gene, E3L, has been shown to be highly attenuated and yet induces a protective immune response against challenge by homologous virus in a mouse model. In this manuscript the NYCBH vaccinia virus vaccine strain was compared to NYCBH vaccinia virus deleted for E3L (NYCBHΔE3L) in a rabbitpox virus (RPV) challenge model. Upon scarification, both vaccines produced a desired skin lesion, although the lesion produced by NYCBHΔE3L was smaller. Both vaccines fully protected rabbits against lethal challenge by escalating doses of RPV, from 10 LD50 to 1,000 LD50. A single dose of NYCBHΔE3L protected rabbits from weight loss, fever, and clinical symptoms following the lowest dose challenge of 10 LD50, however it allowed a moderate level of RPV replication at the challenge site, some spread to external skin and mucosal surfaces, and increased numbers of secondary lesions as compared to vaccination with NYCBH. Alternately, two doses of NYCBHΔE3L fully protected rabbits from weight loss, fever, and clinical symptoms, following challenge with 100 to 1,000 LD50 RPV, and it prevented development of secondary lesions similar to protection seen with NYCBH. Finally, vaccination with either one or two doses of NYCBHΔE3L resulted in similar neutralizing antibody titers following RPV challenge as compared to titers obtained by vaccination with NYCBH. These results support the efficacy of the attenuated NYCBHΔE3L in protection against an orthologous poxvirus challenge.

Background: the behavioral modification stages (BMS) are widely used; however, there are no reports on long-term nutrition counseling for cardiovascular disease (CVD) according to BMS. Aim: to study the effects of long-term nutrition counseling based on the BMS in patients with CVD. Methods: fifteen patients with CVD who participated in nutrition counseling were enrolled between June 2012 and December 2016. We provided BMS and dietary questionnaires to estimate the stage score (SS), salt intake, and drinking habits (non-drinking group (n = 7)/drinking group (n = 8)), and measured the blood pressure (BP), body mass index (BMI), and biochemical markers before and after hospitalization at 6 months, 1 year, and 1.5 years after leaving the outpatient department (OPD). Results: a significant decreased salt intake and increase in SS were found at 1.5 years. It significantly decreased the BP and salt intake in the non-drinking group at 1.5 years. Conclusions: long-term nutrition counseling according to BMS improved salt intake and BP in the non-drinking group. However, in the drinking group, increased salt intake might weaken the BP improvement. Temperance and low-sodium intake are essential factors that control BP, especially in drinkers.

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