Need for validation of vaccination programs

Abstract

The risk of immunodeficiency associated with frequent messenger ribonucleic acid (mRNA) vaccinations has become increasingly evident, leading to the widespread discontinuation of additional doses, except in Japan.
Reevaluation of vaccination programs, including live-attenuated vaccines, is crucial. Recently, three cases of children who died a day after routine vaccination were reported in Japan. Despite detailed information, including autopsy findings, experts concluded that a causal relationship with vaccination could not be evaluated. This commentary highlights the challenges with mRNA vaccines and further discusses the need to reassess the efficacy and safety of vaccines that have already been approved.
In the post-mRNA vaccination era, marked by an increase in shingles cases, it is essential to re-evaluate the risks and benefits of currently approved vaccines.

Full text

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Discover Medicine
Comment
Need forvalidation ofvaccination programs
KenjiYamamoto1
Received: 29 November 2024 / Accepted: 6 March 2025
© The Author(s) 2025 OPEN
Abstract
Background The risk of immunodeciency associated with frequent messenger ribonucleic acid (mRNA) vaccinations
has become increasingly evident, leading to the widespread discontinuation of additional doses, except in Japan.
Main body Reevaluation of vaccination programs, including live-attenuated vaccines, is crucial. Recently, three cases
of children who died a day after routine vaccination were reported in Japan. Despite detailed information, including
autopsy ndings, experts concluded that a causal relationship with vaccination could not be evaluated. This commen-
tary highlights the challenges with mRNA vaccines and further discusses the need to reassess the ecacy and safety of
vaccines that have already been approved.
Conclusion In the post-mRNA vaccination era, marked by an increase in shingles cases, it is essential to re-evaluate the
risks and benets of currently approved vaccines.
Keywords Evaluation· mRNA· Vaccination· Live-attenuated vaccines· Immunodeciency
1 Background
Growing evidence of immunodeciency risks associated with frequent messenger ribonucleic acid (mRNA) vaccina-
tions [1] has led to the global discontinuation of additional doses, with Japan as the notable exception. The decrease
in immunity can be caused by several factors, such as N1-methylpseudouridine, the spike protein, lipid nanoparticles,
antibody-dependent enhancement, and the original antigenic stimulus [1].Subsequent studies showed that a signi-
cant increase in IgG4, which evades immunity, occurs in frequent vaccine recipients, contributing signicantly to the
elucidation of the mechanism of mRNA vaccine-induced immunodeciency [2]. This highlights the need for a compre-
hensive re-evaluation of vaccination programs. Notably, live-attenuated vaccines are contraindicated for individuals
with immunodeciency. Recently, three child deaths were reported in Japan within a day of routine vaccination [3].
Despite detailed investigations, including autopsies, experts were unable to evaluate a causal link to vaccination. This
commentary addresses the challenges related to mRNA vaccines and underscores the importance of reassessing the
ecacy and safety of approved vaccines.
1.1 Current status ofCOVID‑19 andproblems associated withmRNA vaccines
While vaccine development typically requires 7–10years, the coronavirus disease 2019 (COVID-19) pandemic acceler-
ated the process, leading to the rapid development, approval, and distribution of vaccines without extensive animal
* Kenji Yamamoto, yamamoto@okamura.or.jp | 1Department ofCardiovascular Surgery, Center ofVaricose Veins, Okamura Memorial
Hospital, 293-1, Kakita Shimizu-cho, Sunto-gun, Shizuoka411-0904, Japan.

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or clinical trials. Initially, medical staff were prioritized for vaccination based on optimistic projections that vaccinating
90–95% of the population would lead to herd immunity [4].
In Japan, a 26-year-old healthcare worker reportedly died of a brain hemorrhage 4days after receiving a sin-
gle dose of the mRNA vaccine early in the vaccination campaign [5]. This case was potentially linked to vaccine-
induced immune thrombotic thrombocytopenia. Despite this, the vaccination program continued, becoming nearly
mandatory.
The publication of an article on the adverse effects of COVID-19 vaccines in the Virology Journal [1] marked a
turning point, halting further vaccinations worldwide after June 2022. This is because, for the first time, in the peer-
reviewed article, the cause of the immunodeficiency was clearly presented, a request was made to discontinue the
booster mRNA vaccination [1], and the information was spread worldwide through social networking sites and other
means. Although a new type of mRNA vaccine was approved afterward, Japan remains the only country actively
vaccinating its population. Despite the declining number of vaccinators, the routine administration of the eighth
coronavirus vaccine dose for older adults began in October 2024.
Concerns have surfaced regarding the potential increase in IgG4 antibody levels following four or more doses
of mRNA [2], possibly leading to vaccine-acquired immunodeficiency syndrome [6]. Immunodeficiency should be
suspected if lymphocyte counts fall below 1,000/μL in blood tests.
Moreover, there has been a rise in cases of shingles, monkeypox, syphilis, severe streptococcal infections, measles,
sepsis, and post-operative infections in countries administering multiple vaccine doses. Ironically, mRNA vaccines,
initially introduced as a solution for infection control, have instead triggered an increase in infections. In Japan,
excess deaths since the onset of vaccination have exceeded 600,000, though the exact cause remains contentious.
The cause of excess deaths cannot be explained solely by corona-related deaths or an aging population, and the
increase in vaccine-related deaths may be a significant factor [7]. Similar trends are observed in other countries with
intensive vaccination programs [8].
While counting infected individuals and processing statistics related to the coronavirus vaccine, the Ministry of
Health, Labor and Welfare (MHLW) classified some individuals who received two or more doses as unvaccinated. These
data discrepancies have since been addressed, with age groups showing a low infection rate among unvaccinated
individuals. Following this, the ministry stopped releasing the statistics.
Adverse events are most frequent in the 1–2weeks after vaccination, particularly immunosuppression and lym-
phocyte reduction [9], which facilitate infections, especially by coronaviruses. Many reports recommending mRNA
vaccines excluded cases occurring less than 1–2weeks post-vaccination, often classifying them as unvaccinated [10].
Correcting these errors could significantly alter study outcomes.
In Japan, the Health Science Council (Adverse Reaction Review Subcommittee, Immunization and Vaccine Subcom-
mittee) investigates adverse events related to vaccinations. Over 2,200 reports of suspected vaccine-related deaths
have been filed, though this likely represents only a small fraction. The causal relationship between a vaccine and an
adverse event is classified as follows: α (causality cannot be denied), β (no causal relationship found), and γ (causal-
ity cannot be evaluated due to insufficient information). Despite autopsies, over 99% of reported deaths occurring
immediately after vaccination fall under category γ, meaning causality is difficult to determine. Only two cases have
been classified as α, where causality could not be excluded. This raises questions about the effectiveness of the
council. Nonetheless, the government maintains that there are no serious concerns. Further complicating matters,
several council members have received donations from pharmaceutical companies, and consultants are prohibited
from participating in council votes.
Even when causality between a vaccine and an adverse event is unclear, Japan’s vaccination damage compensa-
tion system—operating for almost 47years—has certified over 150 deaths as vaccine-related across more than 20
vaccines, excluding coronavirus vaccines. However, as of December 12, 2024, 932 deaths have been attributed to
the coronavirus vaccine [11], marking a recognized abnormality.
While health ocials in many countries have faced public outrage, Dr. Anthony Fauci has come under intense con-
gressional scrutiny in the United States (U.S.), and lawsuits have been led against Pzer in the U.S. and other countries.
Despite the seriousness of these developments, major Japanese media outlets have rarely covered this information.
1.2 Questions ontheefficacy andsafety ofcurrently approved vaccines
The release of recent vaccines has raised several important questions regarding their licensing process and the accuracy
of methods used to assess vaccine ecacy, such as their ability to prevent severe outcomes. Are the benets of these

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vaccines truly outweighing the risks? Are adverse events genuinely un-evaluable? And could there be undisclosed facts
that need to be considered?
Table1 summarizes recent post-vaccination child deaths reported by the MHLW in Japan. It includes three cases
where deaths occurred within a day of vaccination. In one case, a 2-month-old boy became ill 30min after receiving
simultaneous doses of Hemophilus inuenzae type b, rotavirus, and pneumococcal vaccines. He went into asystole in the
hospital 59min later and died the next day. Details of this case were published on the MHLW website [3]. Additionally, a
6-month-old child who received seven dierent vaccines (hepatitis B; Hemophilus inuenzae type b; pneumococcus; and
a combined four-in-one vaccine for pertussis, diphtheria, tetanus, and polio) and a 3-year-old child vaccinated against
Japanese encephalitis both died the day after vaccination [3].
Despite the availability of detailed reports and autopsies, experts classied all three cases as γ (evaluation not possible),
similar to assessments of deaths following coronavirus vaccinations. This raises concerns regarding possible external
pressures or vested interests inuencing such determinations.
Furthermore, the simultaneous administration of newly developed vaccines—whose adverse event proles may not
be fully conrmed—alongside existing vaccines has been approved. For example, the simultaneous administration of
coronavirus and inuenza vaccines has become common in recent years. This practice raises concerns that promoting
simultaneous vaccination could obscure causal links to adverse events from the outset.
In Japan, vaccines are administered starting at 2months of age. By adulthood in 2024, a child will have received vac-
cines for almost 14 dierent diseases, with doses delivered either individually or simultaneously. The total number of
inoculations increases signicantly when booster doses are included. Vaccinations are categorized as either routine or
voluntary. For minors, vaccines such as mumps, inuenza, and coronavirus are voluntary, while others are routine [12].
Vaccination schedules and contents vary by country, so the total number of vaccinations may dier. Furthermore, apart
from the adverse eects of vaccines, there are also many problems associated with routine immunization in some areas.
It must be considered that various factors, e.g., lockdowns in pandemics, can aect vaccination coverage in developing
countries, sometimes leading to outbreaks of vaccine-preventable diseases [13].
Historically, the inactivated inuenza vaccine was thought to prevent infection, but this assumption was challenged
by the Maebashi Report, leading to its reclassication as a voluntary vaccine. During the spread of a new inuenza strain
in 2009, nearly no one in Japan aged > 40years was infected, while almost everyone aged < 40years was. This phenom-
enon is thought to result from cross-reactive immunity among older individuals who had previously been infected with
earlier inuenza strains and recovered without antiviral drugs [14].
Inactivated vaccines can aect the immune system. Inuenza vaccination, in particular, may further strain the immune
system, which could already be weakened by multiple coronavirus vaccinations. Additionally, the mRNA-type inuenza
vaccine is currently in phase 3 trials [15], and it is possible that in the future, mRNA vaccines for both coronaviruses and
inuenza viruses could be included in the same vial. In such cases, it may be wise for medical institutions to withdraw
their sta from the vaccination program as soon as possible.
Streptococcus pneumoniae is a common bacterium that becomes pathogenic when the immune system is weakened.
A vaccine has been developed to protect against it, and for adults, a vaccine eective against 23 of the approximately
90 serotypes is recommended. However, some hypothesize that this selective vaccination could potentially lead to an
increased prevalence of the remaining serotypes.
In the past, when hepatitis B vaccination failed to generate an eective antibody titer, a booster dose was adminis-
tered. However, the practice of antibody titer testing and subsequent booster administration has since been discontin-
ued. This raises a critical question: if antibody titers naturally decrease over time, is it necessary for all individuals to be
vaccinated in childhood?
Recent vaccines, including those for Japanese encephalitis, cervical cancer, and coronavirus, have shown a low but
signicant risk of serious autoimmune conditions, such as acute disseminated encephalomyelitis and Guillain–Barré
syndrome, as potential adverse events.
The human immune system is remarkably complex, with many mechanisms still not fully understood. The production
of immunoglobulins (antibodies) is inherently limited, and vaccination with a specic antigen does not substantially
increase the immune system’s overall capacity. Humans coexist with a vast array of microorganisms, including over 1,000
types of commensal bacteria, fungi, and viruses [16]. This symbiotic relationship requires constant renewal of immunity.
It is worth considering whether the acquisition of immunity through vaccination, which prioritizes the production
of one type of antibody (e.g., as seen with coronavirus vaccines), might inadvertently reduce the production of others.
As many viruses and bacteria are transmitted through mucous membranes, the current method of directly injecting

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Table 1 Selected cases of child deaths occurring the day following vaccination
Abbreviations: vaccination, Vx; cardiopulmonary arrest; CPA, Haemophilus inuenzae type b; Hib, months; mo, years; yrs
*Notation of the causal relationship between vaccines and the name of the symptom
Α: Causality is undeniable, β: No causal relationship is found, γ: Cannot be evaluated due to lack of information, etc.
Case no Age Sex Primary illness Vaccines Date of vaccination and summarized progress Death
day after
Vx
Autopsy Survey
results*
3 2 mo M none Hib, rotavirus, pneumococcal vaccines Jan. 23, 2024 Sudden illness 30min and went into asystole
in hospital 59min after Vx 1day + γ
5 6 mo F cold symptoms hepatitis B, Hib, pneumococcal, four-in-one
vaccine (pertussis, diphtheria, tetanus,
polio)
Nov. 24, 2023 The day after Vx, she was found dead in
the bedroom. Negative for inuenza and coronavirus
antigens
1day + γ
1 3 yrs M Asthmatic bronchitis
allergic rhinitis febrile
convulsions
Japanese encephalitis vaccine Oct. 27, 2023 Appeared lethargic and had a fever of 39.4°C
approximately 8h after Vx; CPA noted 10h after Vx 1day + γ

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vaccines into the body bypasses natural immune pathways. As vaccines are administered to healthy individuals, their
safety is paramount to ensure they do not contribute to disease or mortality [17].
1.3 Need forvalidation ofvaccination programs andpreventive measures
The Japan Pediatric Society continues to recommend voluntary coronavirus vaccination for infants as young as 6months
old [18]. However, this guideline appears questionable, as once a vaccine is approved, the evaluation of adverse events—
regardless of their frequency or severity—consistently results in a classication of "inability to evaluate" by experts.
Despite this, after weighing the advantages and disadvantages, the Health Science Council concluded that no changes
to the current coronavirus vaccination regimen were necessary.
Japan is the only country globally to have approved a self-amplifying RNA vaccine (commonly referred to as a rep-
licon vaccine) at present (Dec. 17, 2024), and vaccination with this product has already commenced, sparking societal
concern. It seems the Japanese public is now being inadvertently involved in clinical trials to gather data on vaccine
safety and risks.
Globally, questioning vaccination has long been considered taboo, with strong social pressures to conform and be
vaccinated. The aggressive promotion of thecoronavirus vaccine through biased messaging remains vividly remembered.
This atmosphere of conformity may partially explain the lack of signicant progress in critically reviewing vaccination
practices.
Numerous vaccines are currently under development, yet true vaccine advancement requires rigorous methodolo-
gies, including double-blind, placebo-controlled trials with long-term follow-up. Conducting such studies poses ethical
challenges, particularly in an environment where vaccination is universally regarded as unequivocally benecial.
2 Limitations
Vaccination programs are subject to change according to the policies of governments and health agencies of the time.
The situation in Japan is not necessarily the same as the rest of the world. Lymphocyte count is only one indicator of
immune function, and a normal lymphocyte count does not mean that immunodeciency does not exist. Randomized
controlled trials are needed to further conrm these clinical observations.
3 Conclusions
In conclusion, in the post-mRNA vaccination era, where shingles have become prevalent, it is essential to re-evaluate
the risks and benets of the currently approved vaccines. Although the public health contribution of vaccination is
clear, it also needs to be reviewed in order to respond to the current changing circumstances. Documenting the history
of mRNA vaccination [1] and conducting pre-vaccination blood tests are crucial steps to rule out immunodeciency.
Additionally, the department involved in the evaluation and licensing of vaccines should be reassessed, with members
without conicts of interest being re-elected. Furthermore, consideration should be given to temporarily suspending
the current vaccination program to determine the full extent of potential harm.
Acknowledgements The author thanks Masanori Fukushima MD, PhD and Jun Ueda PhD for their invaluable advice in writing this manuscript.
The author thanks Editage (www. edita ge. com) for the English language editing.
Author contributions KY wrote the entire manuscript text and reviewed it. The author read and approved the nal manuscript.
Funding None.
Data availability No datasets were generated or analysed during the current study.

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Declarations
Ethics approval and consent to participate Not applicable.
Competing interests The authors declare no competing interests.
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