Preclinical Study on SARS-CoV-2 Sublingual Vaccine with RBD Antigen and Poly(I:C) Adjuvant in Cynomolgus Macaques

Mucosal vaccine for sublingual route was prepared with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and poly(I:C) adjuvant components. The efficacy of this sublingual vaccine was examined using Cynomolgus macaques. Nine of the macaque monkeys were divided into three groups of three animals; control (just 400 g poly(I:C) per head); low dose (30 g RBD and 400 g poly(I:C) per head); and high dose (150 g RBD and 400 g poly(I:C) per head), respectively. N-acetylcysteine (NAC), a mild reducing agent losing mucin barrier, was used to enhance vaccine delivery to mucosal immune cells. RBD-specific IgA antibody secreted in pituita was detected in two of three monkeys of the high dose group and one of three animals of the low dose group. RBD-specific IgG and/or IgA antibodies in plasma were also detected in these monkeys. These indicated that the sublingual vaccine stimulated mucosal immune response to produce antigen-specific secretory IgA antibodies in pituita and/or saliva. This sublingual vaccine also affected systemic immune response to produce IgG (IgA) in plasma. Little RBD-specific IgE was detected in plasma, suggesting no allergic antigenicity of this sublingual vaccine. Thus, SARS-CoV-2 sublingual vaccine consisting of poly(I:C) adjuvant showed reasonable efficacy in a non-human primate model.

Prevalence of Salivary IgA Reacting with SARS-CoV-2 among Japanese People Unexposed to the Virus

While the COVID-19 pandemic caused by SARS-CoV-2 has posed a threat to public health as the number of cases and COVID-19-related deaths are increasing worldwide, the incidence of the virus infection are extremely low in Japan compared with many other countries. To explore the reason for this strange phenomenon, we hypothesized the high prevalence of "natural" secretory IgA in saliva as mucosal IgA reacting with SARS-CoV-2, and thus surveyed the positivity for, as well as levels of, such reactive salivary IgA in a cohort of Japanese people of a wide range of age. The major findings were that 95/180 (52.78 %) of overall individuals who had not been exposed to SARS-CoV-2 were positive for salivary IgA with the levels ranging from 0.002 to 3.272 ng/ml, and that there may be a negative trend in positivity for salivary IgA according to age. These results suggest a role of mucosal IgA in host defense against SARS-CoV-2 infection. One Sentence Summary"Natural" secretory immunoglobulin A autoantibodies may play a role in mucosal defense against SARS-CoV-2.

Effect of the Deep Sea Shark-liver Oil Component Food on Secretion Type Immunoglobulin A Density of Saliva in the Normal Man and Woman Adult / 日本補完代替医療学会誌

Secretory immunoglobulin A (s-IgA) in saliva constitutes the first-line barrier to the entry of pathogens into the body, implying its critical role in mucosal immunity.To examine the effect of a shark liver oil (SLO)-containing diet on salivary s-IgA concentration in healthy male and female adults, 42 subjects were assigned to either placebo or 6 weeks of a 2,400 mg SLO-containing diet (1,500 mg as SLO) and assessed in a randomized, double-blind, placebo-controlled, parallel group trial.Salivary s-IgA concentration significantly increased at week 6 in the SLO group (P = 0.033), but not in the placebo group.Moreover, there was a significant difference between groups in the magnitude of change from baseline to week 6.No intervention-related adverse event or abnormal changes of laboratory test parameters were observed throughout the study period.In conclusion, an SLO-containing diet increases salivary s-IgA in healthy adults.

Effects of Kaki (Persimmon) Extract-containing Diet on Levels of Volatile Sulfur Compounds in Oral Gas and Feces, as well as on Subjective Fecal Odor, in Healthy Adults / 日本補完代替医療学会誌

<b>Objectives:</b> To examine in two tests the potential of kaki (persimmon) extract-containing diet (KE diet) to reduce malodorous volatile sulfur compounds (VSC), such as hydrogen sulfide (H₂S), methyl mercaptan (CH₃SH) and dimethyl sulfide (CH₃SCH₃), as well as on subjective fecal odor on healthy adults.<br> <b>Methods:</b> In the first test, 11 subjects were given garlic-containing soup. For a period of time, they were given a single dose of KE diet (150 mg as kaki extract) with water, and only water for the rest of the study period. Two hours after the administration, oral gas samples were collected from individual subjects and analyzed for VSC. In the second test, 14 subjects were given a single dose of KE diet for 7 days. Fecal samples were collected from individual subjects before and after the 7-day KE diet intervention. Levels of VSC were determined and the magnitude of subjective fecal odor was estimated based on ratings in the self-administered questionnaire.<br> <b>Results:</b> Levels of CH₃SCH₃ in oral gas were significantly lowered when subjects were on a KE diet. On the other hand, although decreases in the level of any VSC in feces before and after the 7-day KE diet intake did not reach a statistical significance, subjective fecal odor significantly improved by the KE diet intake.<br> <b>Conclusion:</b> KE diet appears to have a beneficial effect on VSC-associated oral malodor and subjective fecal odor.<br>

Acupuncture and moxibustion for patients / 全日本鍼灸学会雑誌

In this report, I trace the life of Prof. Hidetsurumaru Ishikawa who laid the foundation for the present successful development of acupuncture and moxibustion and pursued medical practice based on scientific evidence.<BR>Prof. Ishikawa was born in Toyama Prefecture. After graduation from Tokyo Imperial University, he moved to Kyoto Imperial University to work in Prof. Amaya’s laboratory.<BR>For 4 years starting from 1908, he studied in Europe, mainly under Prof. M. Verworn at Gottingen University, but also briefly visited Prof. I. Pavlov in Petersburg and Prof. E. Starling and Prof. C. Sherrington in England. He learned much about the newest science at that time, and these experiences served as a backbone for his later scientific research.<BR>After returning to Kyoto Imperial University as a professor of physiology, he developed the physiological sciences in Japan. Along with the progression of modern physiology, he came to recognize the need of a scientific approach to traditional medicine, especially acupuncture, as well as a psycho-physiological approach to analyzing human biological conditions. <BR>In the field of neurophysiology, he is famous for a sensational debate against Prof. Kato, who was one of his favorite disciples, about the conduction of electric impulses in anesthetized nerve cells:decrement or decrementless?<BR>After his retirement from Kyoto Imperial University in 1944, Prof. Ishikawa went to Tsu City as the head of Mie Prefectural Medical College, the predecessor of Mie University Faculty of Medicine and opened the department of acupuncture in the university hospital the following year. During the postwar occupation of Japan, the General Headquarters of the Allied Powers (GHQ) decided to prohibit Japanese traditional medicine, because at that time, the general condition of acupuncture and moxibustion therapy in Japan was far below Western standards.<BR>Learning of the prohibition order, Prof. Ishikawa visited the GHQ over and over again to explain with his own data the scientific basis of acupuncture and to demonstrate the benefits of acupuncture to the GHQ medical officers. Probably due to accumulated strain, in 1949 Prof. Ishikawa had a stroke during a faculty meeting and died about 2 weeks later. Prof. Ishikawa was succeeded by his apprentice, Prof. Kyugo Sasagawa of Kyoto University, who organized the Japan Society of Acupuncture. The first conference was held at Kyoto University in 1953, and the society has been continuously developing to its present successful status.

Pulmonary artery banding in early infants with complete atrioventricular canal / 日本心臓血管外科学会雑誌

Infants with complete atrioventricular canal (CAVC) and severe congestive heart failure, not responding to medical managements, presents a difficult management problem. Between December, 1980, and August, 1987, 16 infants with CAVC presenting severe congestive heart failure underwent pulmonary artery banding. Average age at operation was 1.7 months (0.5 to 4) and average weight was 3.5kg (2.5∼4.9). Only four patients were older than 3 months of age at operation. Pre-operative cardiac catheterization and echocardiogram demonstrated that seven patients had mild to severe left atrioventricular valve regurgitation. Hospital death occurred in one patient (6%) due to rupture of the pulmonary artery. Of three late deaths, one patient had congestive heart failure, and one patient complicated with partial obstruction of right pulmonary artery died suddenly of an upper respiratory infection 11 months after rebanding. Survivors have been followed 18 to 94 months and all patients are growing at an increased rate postoperatively. In five patients of 12 long-term survivors who have undergone cardiac catheterization 37 to 83 months after the operation, pulmonary/systemic systolic pressure ratio (<i>PP/PS</i>) were 0.2∼0.42 (average 0.28). It is concluded that the pulmonary artery banding in infants with CAVC can be performed with low operative and late mortality and can provide good relief of symptoms and allow normal growth and development. It should be emphasized that early surgical palliation is mandatory to prevent the development of pulmonary hypertension and pulmonary emphysematous change.