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The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.

IntroductionThis study tested the effectiveness of moxibustion on pain and function in chronic knee osteoarthritis (KOA) and evaluated safety.MethodsA multi-centre, non-blinded, parallel-group, randomised controlled trial compared moxibustion with usual care (UC) in KOA. 212 South Korean patients aged 40–70 were recruited from 2011–12, stratified by mild (Kellgren/Lawrence scale grades 0/1) and moderate-severe KOA (grades 2/3/4), and randomly allocated to moxibustion or UC for four weeks. Moxibustion involved burning mugwort devices over acupuncture and Ashi points in affected knee(s). UC was allowed. Korean Western Ontario and McMaster Universities Questionnaire (K-WOMAC), Short Form 36 Health Survey (SF-36v2), Beck Depression Inventory (BDI), physical performance test, pain numeric rating scale (NRS) and adverse events were evaluated at 5 and 13 weeks. K-WOMAC global score at 5 weeks was the primary outcome.Results102 patients (73 mild, 29 moderate-severe) were allocated to moxibustion, 110 (77 mild, 33 moderate-severe) to UC. K-WOMAC global score (moxibustion 25.42+/−SD 19.26, UC 33.60+/−17.91, p<0.01, effect size  = 0.0477), NRS (moxibustion 44.77+/−22.73, UC 56.23+/−17.71, p<0.01, effect size  = 0.0073) and timed-stand test (moxibustion 24.79+/−9.76, UC 25.24+/−8.84, p = 0.0486, effect size  = 0.0021) were improved by moxibustion at 5 weeks. The primary outcome improved for mild but not moderate-severe KOA. At 13 weeks, moxibustion significantly improved the K-WOMAC global score and NRS. Moxibustion improved SF-36 physical component summary (p = 0.0299), bodily pain (p = 0.0003), physical functioning (p = 0.0025) and social functioning (p = 0.0418) at 5 weeks, with no difference in mental component summary at 5 and 13 weeks. BDI showed no difference (p = 0.34) at 5 weeks. After 1158 moxibustion treatments, 121 adverse events included first (n = 6) and second degree (n = 113) burns, pruritus and fatigue (n = 2).ConclusionsMoxibustion may improve pain, function and quality of life in KOA patients, but adverse events are common. Limitations included no sham control or blinding.Trial RegistrationClinical Research Information Service (CRIS) KCT0000130

BackgroundPersistent non-specific low back pain (PNSLBP) is one of the most frequently experienced types of back pain around the world. Wet-cupping is a common intervention for various pain conditions, especially in Korea. In this context, we conducted a pilot study to determine the effectiveness and safety of wet-cupping treatment for PNSLBP.MethodsWe recruited 32 participants (21 in the wet-cupping group and 11 in the waiting-list group) who had been having PNSLBP for at least 3 months. The participants were recruited at the clinical research centre of the Korea Institute of Oriental Medicine, Korea. Eligible participants were randomly allocated to wet-cupping and waiting-list groups. Following the practice of traditional Korean medicine, the treatment group was provided with wet-cupping treatment at two acupuncture points among the BL23, BL24 and BL25 6 times within 2 weeks. Usual care, including providing brochures for exercise, general advice for PNSLBP and acetaminophen, was allowed in both groups. Separate assessors participated in the outcome assessment. We used the 0 to100 numerical rating scale (NRS) for pain, the McGill Pain Questionnaire for pain intensity (PPI) and the Oswestry Disability Questionnaire (ODQ), and we assessed acetaminophen use and safety issues.ResultsThe results showed that the NRS score for pain decreased (-16.0 [95% CI: -24.4 to -7.7] in the wet-cupping group and -9.1 [-18.1 to -0.1] in the waiting-list group), but there was no statistical difference between the groups (p = 0.52). However, the PPI scores showed significant differences between the two groups (-1.2 [-1.6 to -0.8] for the wet-cupping group and -0.2 [-0.8 to 0.4] for the waiting-list group, p < 0.01). In addition, less acetaminophen was used in the wet-cupping group during 4 weeks (p = 0.09). The ODQ score did not show significant differences between the two groups (-5.60 [-8.90 to -2.30] in the wet-cupping group and -1.8 [-5.8 to 2.2] in the waiting-list group, p = 0.14). There was no report of adverse events due to wet-cupping.ConclusionThis pilot study may provide preliminary data on the effectiveness and safety of wet-cupping treatments for PNSLBP. Future full-scale randomised controlled trials will be needed to provide firm evidence of the effectiveness of this intervention.Trial RegistrationClinicalTrials.gov: (Identifier: NCT00925951)Date of trial registration: June 19th, 2009The date when the first patient was randomised: July 15th, 2009The date when the study was completed: November 27th, 2009

PurposeTo evaluate the effects of acupuncture compared to a control group using artificial tears.Methods Setting & design: multicenter randomised controlled trial (three local research hospitals of South Korea). Study Population: 150 patients with moderate to severe dry eye. Intervention: Participants were randomly allocated into four weeks of acupuncture treatment (bilateral BL2, GB14, TE 23, Ex1, ST1, GB20, LI4, LI11 and single GV23) or to the artificial tears group (sodium carboxymethylcellulose). Main Outcome Measure(s): The ocular surface disease index (OSDI), tear film break-up time (TFBUT), Schirmer Ι test, visual analogue scale (VAS) for self-assessment of ocular discomfort, general assessment (by both acupuncture practitioners and participants) and quality of life (QOL) through the Measure Yourself Medical Outcome Profile-2 (MYMOP-2).ResultsThere was no statistically significant difference between two groups for the improvement of dry eye symptoms as measured by OSDI (MD −16.11, 95% CI [−20.91, −11.32] with acupuncture and −15.37, 95% CI [−19.57, −11.16] with artificial tears; P = 0.419), VAS (acupuncture: −23.84 [−29.59, −18.09]; artificial tears: −22.2 [−27.24, −17.16], P = 0.530) or quality of life (acupuncture: −1.32 [−1.65, −0.99]; artificial tears: −0.96 [−1.32, −0.6], P = 0.42) immediately after treatment. However, compared with artificial tears group, the OSDI (acupuncture: −16.15 [−21.38, −10.92]; artificial tears: −10.76 [−15.25, −6.27], P = 0.030) and VAS (acupuncture: −23.88 [−30.9, −16.86]; artificial tears: −14.71 [−20.86, −8.55], P = 0.018) were significantly improved in the acupuncture group at 8 weeks after the end of acupuncture treatment. TFBUT measurements increased significantly in the acupuncture group after treatment.ConclusionsAcupuncture may have benefits on the mid-term outcomes related to dry eye syndrome compared with artificial tears.Trial registrationClinicalTrials.gov NCT01105221.