Topics Held the Pharmaceutical Manufacturers Association of Japan (PMAJ) Media Forum. Vaccination in the Era of With Corona ~Learning from Pandemics
On December 22, 2021, the "Pharmaceutical Manufacturers Association of Japan Media Forum" was held at the Nihonbashi Life Science Hub (Chuo-ku, Tokyo). The theme of the forum was "Vaccination in the Era of With-Corona: Learning from Pandemics," with a lecture by Dr. Takashi Nakano, Professor of Pediatrics at Kawasaki Medical School. He gave a detailed explanation of how vaccines have contributed to the eradication of infectious diseases on the planet and the correct knowledge that should be possessed in the current with-corona era. Twenty-two journalists participated in the event, both at the venue and via webcast.
The venue
Means to Prevent Infectious Diseases
Through vaccination, people become immune and acquire resistance to pathogens. In the past, measles was a disease that affected a large number of people, and as the Arab proverb says, "Count your children only after the measles are over," there are still expressions related to measles in many parts of the world. Today, however, measles can be prevented by vaccines, and both the number of cases and deaths have been greatly reduced ( Fig. 1 ).
Professor of Pediatrics, Kawasaki Medical School
Dr. Takashi Nakano
Fig. 1 Number of measles cases and deaths reported as cause of death over the past 50 years
The most successful example is the first human vaccine against smallpox by Edward Jenner, from which the name "vaccine" was derived. It took some time after the development of this vaccine, but in 1980, the World Health Organization (WHO) declared smallpox eradicated. One of the dreaded pathogens had been eradicated from the face of the earth. The effect was not only on the health of those who were affected, but also on the many social costs that were reduced, including the nursing and hospital systems of those around them, and the quarantine measures and surveillance established by local communities. The dissemination of the vaccine has these significant social values.
Polio Eradication Plan
On May 5, 2014, WHO declared the spread of wild poliovirus a Public Health Emergency of International Concern (PHEIC). Currently, new coronavirus infections are also considered a PHEIC. The Global Polio Eradication Program began in 1988, and Dr. Nakano was instrumental in implementing the program in Ghana. At that time, polio was endemic in 125 countries and the number of polio cases had reached 350,000. By 2006, the number of polio cases had dropped to 1997 in four polio-endemic countries. However, polio cases in the Middle East and Africa have since begun to increase again due to outbreaks of live vaccine-derived poliovirus strains used in immunizations. In addition to the emergence of these new mutant viruses, the impact of conflict and insecurity on the medical field has also made the polio eradication program more difficult. In some cases, health care staff working on polio eradication have been harmed by negative attitudes toward the vaccine. Thus, the Global Polio Eradication Plan remains on a difficult path, not only because of the scientific challenge of "fighting the virus," but also because of social issues such as security and inequality ( Figure 2 ). In this sense, it may be said that the eradication of smallpox was indeed a stroke of luck.
Fig. 2 Difficult road to polio eradication: two factors
Evaluation of Vaccine Efficacy
Next, let us turn to the new coronavirus. Vaccine efficacy is measured mainly by five indicators, of which "prevention of disease onset" is the most common ( Fig. 3 ). Using this indicator, the effectiveness of vaccines currently in wide use is shown to be highly effective in preventing the onset of disease. In particular, a large-scale study conducted in Israel showed a 97% efficacy in preventing the onset of the disease. This study was conducted within a few months after vaccination, so it is possible that the efficacy may have declined over time, but this may be the first study in human history to examine both vaccinated and unvaccinated individuals on a large scale. Another study on the efficacy of the vaccine in preventing the onset of disease against mutant strains was conducted in the United Kingdom. For the delta strain, the results show that it is still highly effective, although its efficacy is somewhat reduced. The Omicron strain has not yet been the subject of any noteworthy studies, but it has been suggested that the vaccine may be less effective because the Omicron strain has been shown to be more resistant to mutations than the Omicron strain. This is because the Omicron strain has genetic mutations in a number of locations in the spike protein targeted by the current vaccine. At this time, the data are from test tubes and await further investigation.
Fig. 3 Evaluation of vaccine efficacy
Expectations for Collective Immunity Effect
In addition to preventing the onset and severity of disease in affected individuals, vaccines also have an important "herd immunity effect. This is the effect of increasing the number of people who are immune through vaccination, thereby blocking the spread of infection and thereby protecting those who cannot be vaccinated. Unfortunately, it is not known what percentage of people need to be vaccinated to achieve the herd immunity effect, but it is expected to have a protective effect against the spread of infection ( Figure 4 ).
Fig. 4 Expectations for the effect of mass immunity
While vaccination rates are increasing, we often hear stories of people who were vaccinated but became infected. This phenomenon is due to the fact that although the number of affected (infected) persons in the population is decreasing, the number of vaccinated persons is increasing, resulting in an increase in the number of cases of infection among vaccinated persons ( Fig. 5 ). Such cases attract particular attention, and therefore seem to be more common. However, the number of infections has been decreasing due to the increase in the number of people vaccinated. In fact, during the fifth wave, the increase in infections among the elderly was lower than that among other age groups.
Fig. 5 Relationship between vaccination coverage and number of people infected
Vaccine Safety
While there is a lot of information flying around about vaccine safety and adverse reactions, it is important to understand them correctly. What is important is whether the adverse reaction is causally related to the vaccination. In the early days, there were stories of subarachnoid hemorrhage and acute aortic dissection after vaccination. At present, however, there is no evidence that vaccinated people are more susceptible to such symptoms than non-vaccinated people. In addition, one in 3,650 elderly people in Japan is transported to an emergency room each day, regardless of the cause, and approximately one in 10,600 people die each day. Even if a person is rushed to the emergency room within 24 hours of vaccination, it does not necessarily mean that the vaccine is the cause.
In the Phase III clinical trials of each company's vaccine, there was little difference in the frequency of serious adverse events between the vaccination group and the control group. However, these trials were conducted on a scale of 20,000 patients, so it can be said that rare events, such as one in 100,000, were not detected. For example, there was information that thrombosis is more likely to occur with viral vector vaccines. This has been reported to be about 1 in 100,000 to 250,000 vaccinations. Based on this, currently in Japan, the virus vector vaccine is limited to people over 40 years of age. In addition, there was also information that myocarditis and pericarditis can occur. These symptoms, which are also estimated to occur in 1 in 100,000 people regardless of vaccination, have been reported as very rare cases after mRNA (messenger RNA) vaccination. However, even when they do occur, they are often mild, and so far, the benefits of vaccination are considered to be greater ( Fig. 6 ). In both cases, it is important to make decisions based on correct information and take the correct measures.
Fig. 6 Safety of the new corona vaccine - issues for future consideration
Vaccine Hesitancy
Adverse Events Following Immunization (AEFI) are not only reactions to vaccine components, but also anxiety-related reactions. Stress-Related Responses (ISRR). The psychological factors vary and can be influenced by past experiences of pain, negative information from surroundings, etc. In Japan, many AEFIs are caused by the "quiet public" and the "silent public.
In Japan, many people are correctly judged as the "Silent Majority," but there is also a "Vaccine Hesitancy" group, which is considered to be "somewhat" hesitant about vaccination. In addition, we need to be careful about Vaccine Hesitancy by health care workers. For example, some doctors advise against vaccines that use chicken eggs in the manufacturing process, saying, "If you are allergic to eggs, it is better not to use them," but overseas, egg allergies have little effect.
Vaccination of children (5-11 years old)
Some people are concerned about inoculating children with the vaccine. In many cases, children do not show strong symptoms even if they are infected, but the mRNA vaccine has been confirmed to be as effective in preventing the onset of disease (in the 90% range) as in adults. Adverse reactions are also considered to be similar to those in adults, with pain at the vaccination site being the most frequent, and fever being the most common systemic reaction. Comparing data on adverse reactions in children and adults, there is no evidence that they are more frequent or more severe in children. However, the data on which the U.S. approval of vaccination for children was based is still limited to a few thousand cases, so it is possible that the risk of serious adverse reactions, which occur infrequently, has not yet been detected. Therefore, it is necessary to monitor the data that will be accumulated overseas, and to continue monitoring safety in Japan as well.
Since the amount and concentration of antigens to be inoculated into children are different from those of the adult formulation, it is essential that information be shared in advance so that no mistakes are made at the site of inoculation. In addition, it is necessary to discuss whether individual inoculation should be the basic method or whether mass inoculation at schools and other facilities should be conducted. Furthermore, it is necessary to have an emergency system that can respond to children with symptoms of suspected adverse reactions, including at night and on holidays. With regard to vaccination of children, there is also debate as to whether it is necessary to take the risks associated with the vaccine while the possibility of serious illness due to infection is low. Further discussion is needed to consider the balance between the risk of infection and the usefulness of the vaccine ( Fig. 7 ).
In this sense, the vaccination of pregnant women has been the subject of "vaccination recommendations," but while vaccination had not progressed well, the unfortunate case that occurred in Chiba led to the spread of vaccination at a rapid pace. The legal status of the vaccination differs from how individuals perceive it. In the end, it is important for each individual to consider both the risks and benefits for themselves.
Fig. 7 Balance between the risk of infection and the usefulness of the vaccine
Closing Remarks
This media forum took place at a time when the Omicron strain of the new coronavirus was beginning to spread. More than two years have already passed since humans were first infected with the novel coronavirus, and various medical findings have been accumulated. Through this lecture, I was able to reaffirm the importance of disseminating information on the role and effects of vaccines by conveying medical findings in a correct and easy-to-understand manner so that people can make appropriate judgments on their own, alleviating some of their concerns.
( Ikuno Fujii, Media Relations Subcommittee, Public Relations Committee)