Vaccines trace their history back hundreds of years. The finding in 1774 that
exposure to cowpox, a virus that can spread from cows to humans, could protect a
person against smallpox, is said to have led to the discovery of vaccines two years
later. In 1776, English physician Edward Jenner injected cowpox virus in the arm of a
boy, who when later injected with smallpox virus, remained healthy and went on to
become the first person to be successfully injected against smallpox. Dr. Jenner is
said to have coined the term ‘vaccine’, from the Latin word for cow, ‘vacca’.
As early as the 15th century, people attempted to prevent illness by
intentionally exposing healthy people to disease-causing ‘germs’. The practice, later
known as variolation following the discovery of a vaccine for smallpox by Dr. Jenner,
comes from the French word for smallpox, ‘la variole’. By today’s standards, the use
of variolation by Dr. Jenner to develop the smallpox vaccine will be considered
‘unethical’ and ‘medically unacceptable’.
But then, it is the practice of variolation that lies behind the discovery of most
vaccines we take for granted today. And, there is no denying that vaccines have
saved more human lives than any other medical invention in history.Today, for
For most vaccine testing purposes humans have been replaced by rabbits, rats,
monkeys, or other non-human ‘guinea-pigs’ — which supposedly make the
practice a ‘more ethical’ method.
Despite these controversies, vaccines are currently the ‘go-to’ norm in preventing
infection from most deadly diseases. Not only do vaccines work effectively in most
people, they also can be produced in the millions on short order during medical
emergencies — provided such a vaccine is available.
Although vaccines work well in most scenarios, they are not perfect and could work
even better with a little help. Researchers at Stanford University in the United
States now appear poised to offer that ‘little help’. In a recent breakthrough
research, scientists at Stanford developed a new vaccine helper that combines two
kinds of adjuvants — ingredients that improve a vaccine’s efficacy — in a novel,
customizable system.
In lab tests, the experimental additive improved the effectiveness of COVID-19 and
HIV vaccine candidates and it could even be adapted to stimulate immune
responses to a variety of pathogens. The researchers say their new discovery could
potentially be used one day to fine-tune vaccines for vulnerable groups like young
children, older adults, and those with compromised immune systems.
Current vaccines are not perfect, as many fail to generate long-lasting immunity or
immunity against closely related strains such as flu or COVID-19 vaccines. One way to
improve them is to design more potent vaccine adjuvants. Combining different
adjuvants to enhance the immune-stimulating effect is an area of research that is
increasingly gaining significance.
For their tests, the research team developed sphere-shaped nanoparticles made of
saponins — immune-stimulating molecules common in adjuvant development. To
these nanoparticles, they attached toll-like receptor (TLR) agonists — molecules
that stimulate a variety of immune responses. They then tested the new adjuvant
platform in COVID and HIV vaccines, comparing it to vaccines containing alum
(aluminum hydroxide) — a widely used adjuvant.
The new nanoparticle-adjuvanted vaccines were found to trigger stronger, longer–
lasting effects. Notably, the combination of the new adjuvant system with a SARS–
CoV-2 virus vaccine was effective in mice against the original SARS-CoV-2 virus and
against Delta, Omicron, and other variants that emerged in the months and years
after the initial outbreak.
TLR agonists] are a highly valuable tool in the vaccine toolbox. They activate the
innate immune system, putting it on a heightened alert state that can result in
higher antibody production and longer-lasting protection. Different combinations
activate different parts of the immune system. TLR agonists have also shown
promise against Alzheimer’s disease, allergies, cancer, and even addiction. An
experimental immunotherapy using TLR agonists for advanced solid tumors has
just entered human trials.
In the Stanford study, researchers tested five different combinations of TLR
agonists hooked to the saponin nanoparticle framework. Based on which TLR was
activated, each elicited a slightly different response from the immune cells.
Ultimately, the latest advance is expected to spur the development of vaccines
tuned for stronger immune protection. The customizable aspect of TLR agonists is important too. The human immune
system changes dramatically from birth to childhood into adulthood into older
maturity.
It is not a one-size-fits-all. Vaccines need to be tailored to these
populations for maximum effectiveness and safety. Combining a saponin with a TLR
agonist has found success before. The live attenuated yellow fever vaccine, given to
more than 600 million people around the world and considered one of the most
powerful vaccines ever developed, uses several TLR agonists.
The nanoparticle platform could also easily be used to test different TLR agonist
adjuvant combinations in vaccines. “We now have a single nanoparticle adjuvant
platform with formulations containing different TLRs, scientists can pick which
specific formulation is the most suitable for their needs,” said the Stanford team.
However, the researchers added that their discovery was still a long way off from
becoming readily available for human use. The success of tests on mice will first
need to be replicated in larger animals and then in rigorous clinical trials. This could
likely be the next step that the researchers will be looking into.
