Contrary
to the long-held belief that the effects of vaccines are specific
for the disease they were created; compelling evidence has
demonstrated that vaccines can exert positive or deleterious
non-specific effects (NSEs).
Analysis
of information showed that live vaccines induce positive NSEs,
whereas non-live vaccines (Covid) induce several negative
NSEs, including increased female mortality associated with
enhanced susceptibility to other infectious diseases, especially
in developing countries.
These
negative NSEs are determined by the vaccination sequence,
the antigen concentration in vaccines, the type of vaccine
used (live vs. non-live), and also by repeated vaccination.
We do not recommend stopping using non-live vaccines, as they
have demonstrated to protect against their target disease,
so the suggestion is that their detrimental NSEs can be minimized
simply by changing the current vaccination sequence. High
IgG4 antibody levels generated in response to repeated inoculation
with mRNA COVID-19 vaccines could be associated with a higher
mortality rate from unrelated diseases and infections by suppressing
the immune system. Since most COVID-19 vaccinated countries
are reporting high percentages of excess mortality not directly
attributable to deaths from such disease, the NSEs of mRNA
vaccines on overall mortality should be studied in depth.
Introduction
Human
vaccines were created to protect against infectious diseases
such as measles, smallpox, polio, and tuberculosis. Edward
Jenner (1749–1823) is generally referred to as father
of vaccination technology, as his smallpox vaccine heralded
the era of vaccination as a major preventive therapeutic strategy,
which eventually culminated in the eradication of smallpox.
It is often not highlighted that Jenner’s small pox
vaccine and all those who followed fitted within the framework
of the “magic bullet” concept in chemotherapy
given later by Paul Ehrlich (1854–1915). Jenner’s
first use of cowpox virus clearly indicated that vaccines
can result in collateral advantages in diseases other than
those which results from the pathogen, which is used for the
design of the vaccine. The functioning of the biological world
has classically been viewed and interpreted in terms of the
biological specificity at the cellular and molecular levels.
In the context of enzymes and antibodies, the specificity
concept changed to accommodate “cross-reactivity”.
Recognition of this trait quite early has resulted in our
not especially concerning ourselves with immune response to
cowpox virus protecting against smallpox virus.
The
“lock-and-key” hypothesis has been the anchor
of the one structure – one biological function paradigm,
which has had overarching impact on our views on the way biological
specificity operates in both in vivo and in vitro worlds of
biological systems. Over the time, all this has turned out
to be over-simplification. For example, proteins can be highly
non-specific as seen in the phenomena of protein promiscuity
and moonlighting. These phenomena have been exploited in drug
designs and have led to the concept of drug repurposing. Hence,
it is not surprising that even vaccines turn out to be non-specific
in the sense of influencing immune responses of the diseases
for which they were not designed. Just to be unambiguous,
these non-specific effects are not based upon cross-reactivity
of antibodies etc. They are seen in diseases which are, unlike
cowpox and smallpox, quite unrelated.
In
more recent times, these non-specific effects have assumed
great importance with wider perspectives. This overview is
about the lack of specificity observed with many vaccines
which is generally described as ‘’Non-specific
effects’’ (NSEs) of vaccines. We also discuss
that while looking at NSEs, we get drawn into the hugely controversial
and debatable issue of using live attenuated viruses vs. killed
(inactivated) viruses as vaccines. This debate has not still
ended and continues to impact policy decisions in many countries
in the world. This debate started seriously in the case of
Polio and now has got enmeshed with the discussion on NSEs
of vaccines. NSEs of vaccines have also raised few other questions,
which merit a closer attention. We hope that an updated information
and a critical look at NSEs in this review would be helpful
in future vaccination programs.
An
interesting pattern appeared in which the effects of live
attenuated vaccines and non-live vaccines differed. The live
attenuated vaccines have generally positive non-specific benefits
that are noticeable when they are the most recent immunization.
For instance, African children who were injected with live
vaccines had much lower all-cause mortality than children
who did not, and this disparity cannot be explained by variations
in mortality resulting from the infection.
As
opposed to live vaccines, non-live vaccines, while protecting
against the disease for which they were designed, in some
circumstances may also enhance the risk of other diseases,
especially in females. For instance, in low-income environments,
girls who received the non-live diphtheria-tetanus-pertussis
(DTP) vaccine died at a rate that was 1.5–2 times greater
than girls who did not receive the vaccine, and a comparable
enhanced risk above that of male recipients of the DTP vaccine
Significantly
favorable NSEs have been linked to four live vaccines. An
early intriguing observation was that the high antigen concentration
(with more than 104.7 plaque-forming units) in the high titer
measles vaccine (HTMV), which is also a live vaccine, induced
detrimental NSEs. In addition, the standard measles vaccine
(MV), which had 103 to 104 plaque-forming units, induced more
significant beneficial NSEs for females, whereas HTMV was
linked to higher female mortality.
People
who received 2 or more shots of the COVID-19 mRNA vaccines
have been reported to have unusually elevated concentrations
of IgG4 antibodies, according to recent studies. It has also
been shown that the HIV, malaria, and pertussis vaccines elicited
higher-than-normal IgG4 production, which has been related
to decreased protection against infections.
CONCLUSIONS
The
current vaccination model presupposes that vaccines only provide
protection against a specific infection, that effective vaccines
diminish mortality concerning the proportion of all deaths
attributable to the target infection, and that the outcomes
of vaccines are the same for both boys and girls. Epidemiological
vaccine investigation, nonetheless, has produced findings
that defy these presumptions and imply that vaccines have
significant non-specific impacts on population health.