Growing vaccine hesitancy should be blamed on vaccine developers, regulators, and public health authorities, not on so-called anti-vaxxers.

Based on the alarming safety and efficacy concerns associated with the COVID-19 vaccines, vaccine hesitancy is rapidly increasing, with a growing segment of the population viewing vaccines as detrimental rather than beneficial to human health.

The large-scale implementation of COVID-19 vaccination during ongoing exposure to the rapidly spreading SARS-CoV-2 virus has significantly contributed to this erosion of public trust in vaccines. Although vaccinology is rooted in empiricism, no vaccinologist ever thought that regulatory authorities would approve large-scale human experimentation using entirely new, non-sterilizing, and inadequately tested vaccines in an attempt to control a pandemic. Any serious and experienced vaccinologist must therefore acknowledge that the COVID-19 mass vaccination campaign simply violated some of the most basic scientific principles of vaccinology.

Despite this unprecedented example of poor vaccine practice, we as vaccinologists must acknowledge that even traditional, non-mRNA-based vaccines can cause adverse effects and significant health issues, particularly when they are inadequately designed, insufficiently tested, or improperly deployed. Like many medical interventions, vaccines are not perfect and the optimistic portrayal by mainstream narratives is not always aligned with reality. However, the intrinsic limitations of vaccines do not discourage me as a vaccine expert; rather, they open my eyes and motivate me to strive for better—more effective and safer—solutions.

Claiming, for example, that vaccines, which largely aim to mimic the induction of natural immune responses (i.e., responses known to occasionally cause immunological disorders), are incapable of causing pathological side effects is inherently unreasonable. This is akin to warlords declaring absolute victory in war without admitting any losses in battle; no party can fight a war without casualties (I deliberately use this analogy as strategies from warfare are typically employed to illustrate how our immune system combats pathogenic agents).

While prophylactic vaccines may safely protect individual recipients, they may have detrimental consequences when administered to an entire population that is exposed to a circulating pathogen (e.g., a virus causing an epidemic or pandemic). Hence, mass vaccination must always be approached with extreme caution and underpinned by comprehensive risk-benefit analyses. This is particularly important in the context of infectious epidemics or pandemics in human and non-human animal populations. For humans, however, informed consent is paramount. Unless ethical principles are abandoned, the requirement for informed consent already renders mass vaccination an unacceptable public health strategy. Moreover, there is no evidence that mass vaccination has ever successfully controlled epidemics or pandemics caused by acute, self-limiting infections. Only mass immunization resulting from natural pathogen transmission has achieved this. Natural infection stimulates both innate, cell-mediated immunity (ICMI) and adaptive immunity. While this dual activation generates herd immunity, traditional vaccines failing to stimulate innate, cell-mediated immunity (ICMI) inevitably fail to control ongoing epidemics or pandemics. Even "modern" vaccines, regardless of their technological sophistication, cannot prevent viral infection or reduce viral transmission when deployed during an active epidemic. Thus, it was not only scientifically incorrect but also entirely unethical to claim that mRNA vaccination during the Covid-19 pandemic would help protect others.

Nonetheless, there is one significant exception where vaccines can meaningfully mitigate viral outbreaks:
live-attenuated (replicating) vaccines. These traditional technologies have been used to prevent outbreaks of childhood diseases (e.g., measles, mumps, rubella, varicella) by filling gaps in herd immunity, particularly in areas with large cohorts of newborns. Unlike non-replicating "modern" vaccines, live-attenuated vaccines stimulate innate immune cells (such as Natural Killer cells), which likely explains their continued use despite all modern advances in vaccine technology. However, live-attenuated vaccines are not without risks. On rare occasions, they can cause severe disease, especially in individuals with underlying health conditions or compromised innate immune systems. This also explains why they are typically not administered to older adults. As the elderly are particularly vulnerable during pandemics affecting immunologically naïve populations (e.g., the Covid-19 pandemic), live-attenuated vaccines are contraindicated for pandemic control.

Given these considerations, it is crucial to transparently inform the public that, although live-attenuated vaccines can be lifesaving under certain conditions, they carry inherent risks. This means that the vast majority of immunologically naïve children, especially when living in highly crowded areas with poor hygienic standards, will typically benefit from routine childhood vaccination upon viral exposure, while rare cases of vaccine-induced side effects or disease cannot be ruled out. This is precisely the purpose of informed consent. It is essential that the information provided to the public also includes information about both the risks and benefits applicable at the population level, acknowledging that each individual is indeed a part of the population.

No one should ever be coerced into vaccination. Rather than stigmatizing and denigrating those who refuse the shot— often because they have educated themselves and ask difficult questions rather than blindly adhering to dogmas— so-called “vaccine experts” and public health experts should deepen their understanding of how the immune system functions and evolves in response to environmental factors. In line with evolving scientific insights, I have repeatedly advocated for a shift from "foreign-centered" to "self-centered" immunization strategies. Rather than focusing solely on antigen-specific B- and T-cell responses, "self-centered" approaches enable antigen-presenting cells to enhance the presentation of immune-subversive, pathogen-derived, self-mimicking peptides, thereby improving their recognition by MHC-unrestricted Natural Killer (NK) cells. This method closely mimics the immune education of NK cells achieved through repeated exposure to live pathogens (including live-attenuated ones), without carrying the risk of causing productive infection. Although (or: because?!) this pathogen-nonspecific approach would target multiple pathogens at once—similar to how antibiotics address a broad range of bacteria— the vaccine industry has not shown any interest in pursuing NK cell-based immunization strategies. Furthermore, too much emphasis is placed on vaccines targeting young and healthy individuals against acute, self-limiting infections ("low-hanging fruit"), while progress in developing therapeutic vaccines for chronic infectious or non-infectious, immune-mediated diseases (including cancer) has been extremely disappointing.

I welcome the voices of those who critically question and challenge vaccinology. Rather than dismissing them as "anti-vaxxers" and resorting to rhetoric reminiscent of racism, vaccinologists and regulators should engage in informed dialogue and use these discussions to drive innovation that serves societal needs, rather than acting as puppets for the vaccine industry or prestigious research institutes.

The examples presented above demonstrate that vaccinology is fundamentally about understanding biology and immunology, not merely about deploying innovative technologies like mRNA-based vaccines (which should in fact rather be regarded as gene therapy products). Like many drugs, vaccines can have detrimental health effects if not designed, tested, and used according to sound scientific principles. Hence, there is an urgent need to scrutinize the empirical approach that has traditionally guided vaccine development and to present a balanced, evidence-based analysis of vaccine-associated risks and benefits. Such an analysis would foster the humility needed when intervening in one of the body's most complex systems: the immune system.

If we want vaccines to remain credible immune interventions and not be dismissed as instruments of a conspiracy against humanity, we must avoid being dazzled by the sophistication of vaccine-enabling technological advancements and remain open and transparent about their biological limitations and the challenges to educating the immune system in ways that don’t enable immune pathology or pathogen immune escape.

The COVID-19 crisis has demonstrated that even so-called "scientific truth," as typically claimed by prestigious peer-reviewed journals, can be compromised when dominated by orchestrated narratives. The key lesson from the history of vaccines is clear: vaccinology is still far from being the so-called holy grail of immune intervention. Hence, if we recognize that there is still significant room for improvement, we must commit to taking informed consent and unbiased scientific communication seriously to ensure that no harm is done to those who trust us to safeguard their health and that of their loved ones. Blaming individuals and placing personal or institutional interests above respect and dignity will only further erode trust in vaccinology and medicine in general.

Vaccinology is an incredibly rich and multidisciplinary field; we should approach it with a critical, open mind and foster challenging scientific debates aimed at expanding our understanding of how to educate the immune system in ways that are safe and effectively (i.e., “inescapably”) prevent the infectious pathogen from replicating or prevent immune-pathologically altered host cells from proliferating.

Summary and conclusions

The widespread safety and efficacy concerns related to COVID-19 vaccines have significantly increased vaccine hesitancy, with a growing portion of the population perceiving vaccines as harmful rather than beneficial. The mass vaccination campaign during ongoing SARS-CoV-2 transmission has contributed to public distrust, deviating from traditional vaccinological principles.

Vaccinology, rooted in empirical science, was never intended to involve large-scale, poorly tested, non-sterilizing vaccines for pandemic control. Serious experts must acknowledge that the COVID-19 vaccination program departed from sound scientific practice. Nonetheless, it is recognized that any vaccine can cause undesirable immunological effects, especially when improperly designed or implemented.

Prophylactic vaccines are not suitable for mass vaccination during an ongoing epidemic or pandemic. Mass vaccination strategies must, therefore, always be scrutinized, especially in the context of infectious disease outbreaks. As informed consent is a non-negotiable ethical standard, it should, in principle, render large-scale vaccination programs targeting all segments of the population unacceptable. Contrary to public messaging during the COVID-19 crisis, mass vaccination has never successfully controlled pandemics caused by acute, self-limiting infections. Natural infection, stimulating both innate and adaptive immunity, remains the key mechanism for establishing herd immunity against acute, self-limiting infections. This already explains why live-attenuated vaccines represent an important asset to maintaining or restoring the population’s immune protection under specific conditions. However, live-attenuated vaccines are not without risks and are generally unsuitable for pandemic control when the elderly represent the most vulnerable target population.

The need for transparent communication regarding vaccine risks and benefits is critical. Coercive vaccination policies undermine public trust and ignore the complex biological realities of immune system function. Rather than stigmatizing skeptics, the scientific community should engage in open debate and explore vaccine strategies that avoid pathogen immune escape while improve vaccine safety. A shift from "foreign-centered" to "self-centered" immunization, focusing on training the innate immune system without risking productive infection, offers a promising but underexplored avenue of innovation. Unfortunately, due to lack of commercial interest, the vaccine industry largely ignores this avenue.

Finally, the COVID-19 crisis revealed the susceptibility of the scientific establishment to narrative-driven bias. Vaccinology, while a rich and multidisciplinary science, is still far from the "holy grail" of immune intervention, despite efforts by the vaccine industry and other stakeholders to portray them as such. Maintaining humility, prioritizing informed consent, and committing to unbiased, evidence-based science are essential to restoring public trust and advancing the field responsibly.

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