In the 1970-80s, Japan developed various vaccines ahead of the rest of the world. DPT vaccine (diphtheria, tetanus, and pertussis) and Japanese encephalitis vaccine were introduced abroad from Japan. In addition, the Japanese Oka strain used for varicella vaccine is the only strain recommended by the World Health Organization (WHO). However, problems related to vaccination such as aseptic meningitis with MMR (measles-mumps-rubella vaccine) subsequently occurred. As a result, in Japan in the 1990s, new vaccines were not developed and vaccination policy stagnated. On the other hand, many countries around the world promoted vaccination policies from the viewpoint of preventive medicine and developed various vaccines that were incorporated into routine immunization. However, the vaccine gap in Japan has begun to improve recently. Specifically, vaccines that are recommended increased in number and the immunization schedule became complicated. In terms of the past and present vaccination policies in Japan, this session gives an outline of the effects of vaccines and issues regarding vaccines and immunization schedules. Unfortunately, rubella was prevalent in Japan last year, and cases of congenital rubella syndrome have increased. Therefore, we must provide education on the importance of vaccination and herd immunity in Japanese vaccination policy.

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Infectious diseases related to vaccines are defined as ‘preventable diseases’ by the WHO. Although rubella is a preventable disease, an outbreak of it occurred in 2012 in Japan. The number of reported patients was as high as 14,357 and subsequently 32 babies with congenital rubella syndrome (CRS) were born. There is a notable background to this outbreak of rubella, including the history of rubella vaccination, which needs to be understood.
In Japan, rubella vaccine was first administered in 1976 for only girls in junior high schools. Although MMR vaccine was started for both boys and girls in 1989, it was canceled in 1993 due to anxiety about its side effects, such as aseptic meningitis. Although it was started again in 1995, there were gaps in some adults between 20-40 years old who could not receive a vaccine and who have an elevated risk of rubella infection. At the time of the above-mentioned outbreak, this population led to an increase in the number of patients. The importance of rubella vaccine was thus confirmed.
Hepatitis B is one of the major vertically transmitted infections because we reduced the number of HB patients by using better transfusion systems. In 2013, the government changed the protocol to prevent vertically transmitted infection of HBV, which will be more effective for prevention.
Influenza vaccine is the most commonly administered vaccine during pregnancy due to its immunotolerance. It is known that influenza vaccine can be given safely throughout pregnancy, and there are some additional effects.
Finally, a recently investigated vaccine is one for cytomegalovirus (CMV). CMV infection during pregnancy induces congenital CMV infection with neurodevelopmental insufficiency and deafness. Although the rate of positivity for CMV antibodies in adults was previously as high as 90%, it decreased to around 65% for environmental reasons. Manufactured CMV vaccine is in a phase II clinical trial. There will thus be some delay before its potential use in clinical practice. This paper is intended as a review of the history of vaccination and confirmation of the efficacy of vaccines in clinical practice.

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Cancer immunotherapy is currently recognized as the fourth most common therapy for cancer, after surgery, radiotherapy, and chemotherapy. Cancer vaccination is a therapeutic approach that involves attacking cancer cells by enhancing the immunity of cancer patients. The use of cancer immunotherapy to induce a therapeutic antitumor immune response in the patient has huge potential for complementing traditional cancer therapies.
Tumor antigens have been identified in a variety of carcinomas. Since the recognition of cancer-associated antigens by cytotoxic T cells (CTL) was first reported by Van der Brugeen et al. in 1991, numerous clinical trials have been conducted to demonstrate the efficacy of cancer vaccination. In 2010, the US Food and Drug Administration (FDA) approved the vaccine Sipuleucel-T (Provenge®) for the treatment of prostate cancer. Ipilimumab (Yervoy®) is an anti-CTLA-4 antibody preparation that targets cytotoxic T-lymphocyte antigen 4. In 2011, Ipilimumab was approved in both Europe and the USA for the treatment of malignant melanoma. As a result, cancer immunotherapy has attracted attention worldwide, including in Japan.
Peptide vaccination, which is one form of cancer immunotherapy, is a promising approach in which a clinical response is expected. Activated CTLs, which are antigen-specific, are generated using the human leukocyte antigen (HLA) -restrictive epitope peptide derived from a tumor antigen identified by exhaustive gene analysis. In Japan, peptide vaccination is a form of therapy that is currently the focus of intense research.
Cancer vaccination is a therapy that can offer prolonged overall survival whilst maintaining quality of life. However, the efficacy of cancer vaccination has not yet been proved, with the exception of for particular malignant tumors. If a biomarker for responders of cancer vaccination can be discovered, the efficacy of cancer vaccination should be established. We anticipate the results of an investigation by clinical trials using cancer vaccination.

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When it comes to vaccination, you might have heard about Edward Jenner when you were students. Based on experimental findings revealing that individuals with a history of cowpox virus infection were less likely to be infected with smallpox, and smallpox infection only led to mild infectious symptoms without resulting in death, researchers investigated the application of vaccines to treatment. It appears that experiments performed by other physicians caused numerous deaths. Jenner vaccinated humans against smallpox using cowpox virus. This attempt, currently referred to as vaccination, has proved to be successful and saved many people’s lives. Consequently, in May 1980, the WHO declared that smallpox had been eliminated.
Thus, appropriately used vaccination is highly effective and markedly benefits society. However, I think that we need to obtain accurate information on vaccination, such as the individuals for whom each type of vaccination should be indicated, the timing of its use, its limitations, and side effects. As is the case with any drug, no vaccine achieves the same effects in every person, and the beneficial and side effects of vaccines may differ according to each individual’s immune state. The purposes of vaccine use also differ according to the target person and area.
In vaccination, foreign substances (nonself antigens) that do not exist in the human body are administered through the skin, nose, or mouth, or using intramuscular or intravenous injections, in order to induce the involuntary activation of an individual’s immune function. In other words, vaccine is the key player to perturb the immunological milieu and therefore initiates break tolerance.
Therefore, vaccination may cause severe side effects, which are sometimes fatal.
In this public lecture on vaccination, other speakers have reported the latest relevant information, but I will describe the neurological side effects of influenza vaccine. I am also going to talk about the neurological side effects of cervical cancer vaccine, which has been a hot topic in Japan recently, the new reporting system in post-vaccination inflammatory CNS demyelinating event such as ADEM, and the history of therapeutic vaccination against multiple sclerosis, which is my main research theme. Also I discuss the failed vaccination trial against Alzheimer's disease, which is becoming increasingly prevalent worldwide, including Japan. I enclosed lead out in these studies, and how to tackle issues associated with vaccination, whose frequency is expected to increase globally. We have learned that a risk (疫eki; plague ) and a benefit (益eki; value) are two sides of the same coin. To protect ourselves from disease, we need to properly understand immunity and excessive immunological responses.

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We report an investigation of procedures and adaptations of laparoscopic cholecystectomy, including single-port type (TANKO-LC), carried out in our hospital, in order to perform TANKO-LC safely. Twenty-eight cases of laparoscopic cholecystectomy from February 2011 to July 2012 were examined in 3 separate periods: February-July 2011 (initial introduction of TANKO-LC), August 2011-January 2012, and February-July 2012. From the results of the study, in 14 cases of laparoscopic cholecystectomy performed in one year from August 2012, surgical time, amount of bleeding, and length of stay were analyzed. We evaluated the validity of the adaptation of LC. Surgical time was shortened from the middle of three studied periods. However, it was prolonged in the third period. The amount of bleeding also increased in the third period. No significant differences were observed in postoperative hospital stay. For positive cholecystography cases in preoperative DIC-CT examination, surgical time was 102.6 ± 20.4 minutes, but it was 113.7 ± 25.6 minutes in negative cases, showing a significantly prolonged duration of surgery. Therefore, we conducted four-hole-type LC in cholecystography-negative cases and TANKO-LC in 14 cholecystography-positive cases of cholelithiasis in one year from August 2012. As a result, compared with 98.9 ± 18.5 minutes in five cases of the four-hole type, the average surgical time of nine cases with TANKO-LC was 83.0 ± 5.7 minutes, which was significantly shortened. We think that TANKO-LC can be considered a useful standard surgical procedure in laparoscopic cholecystectomy in the future.

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