The "anti-cancer weapon" they created has brought a safer life to countless women

There are more than 500,000 new cases of cervical cancer worldwide each year

Although the overall protective effect of HPV will not be visible until at least 2030, in some countries with higher vaccination rates, preliminary data has shown that vaccines can reduce the proportion of people suffering from cervical cancer

It has only been more than 40 years since humans first linked cervical cancer with HPV in the 1980s, until scientists found a strategy for making HPV vaccines, and then reached HPV vaccines that can be vaccinated

Find the enemy

The first protagonist of this story is Harald zur Hausen

By the time he graduated from high school, Hausen followed his passion for major choices, but made a little change, from biology to medicine

There, he received a lot of basic research training in bacteriology and virology, and his first contact was the effect of vaccinia virus in mouse cells

When he was a postdoctoral fellow, he came to the United States, where virus research is relatively mature, and worked in the laboratory of immunologist Werner Henle

Inspired by this, Hausen continued to explore the relationship between EBV and Burkitt’s lymphoma while studying some of the secret effects of adenovirus in infecting cells

With the research experience on the connection between viruses and cancer, he returned to Germany, and the battle for cervical cancer began

But Hausen found a small flaw in the cornerstone of this theory

At this time, he found some reports that condyloma acuminata can transform into squamous cell carcinoma, and human papilloma virus particles can be detected in condyloma acuminatum

▲HPV under electron microscope (Image source: CNX OpenStax, CC BY 4.

By the end of 1979, Hausen worked with colleagues and finally isolated HPV-6 from condyloma acuminatum for the first time, but they did not detect HPV-6 in cervical cancer samples

This time, 1 out of 24 cervical cancer samples showed positive for HPV-11

This is the first time that Hausen and colleagues have witnessed evidence of a connection between cervical cancer and HPV

In the following two years, more evidence showed that these two viruses played an important role in the progression of cervical cancer

At this point, half of the work to fight cervical cancer has been completed, and we know what to deal with.
What is needed next is a vaccine that can arouse the immune system's vigilance
.

Defend against the enemy

At that time, live attenuated vaccines have achieved significant positive results in the prevention of measles and mumps, but there is a great risk in producing HPV vaccines in this way.
After all, even after attenuated HPV, it still contains and promotes cancer.
Genes that occurred
.
Douglas Lowy and John Schiller of the National Cancer Institute wanted to create an HPV16 vaccine that could only contain non-carcinogenic genetic material
.

At this time, the viral coat protein has become a potential candidate
.
Some proteins on the surface of the virus can reassemble themselves in a test tube in vitro, and can eventually become particles that look the same as the virus
.
Such virus-like particles can cause an immune response, but are safer because they do not contain the genetic factors of the virus
.

Lowy and Schiller believe that HPV has proteins L1 and L2 that may achieve this goal
.
In 1991, immunologist Ian Frazer found in a test that when L1 and L2 were mixed at the same time, HPV16-like virus particles could be produced
.
However, using one protein alone will not succeed
.

By observing the electron microscope, they identified this virus-like particles will be smaller than other papilloma virus particles, so it may be a "complete lack of assembly"
.
Initially, when Lowy and Schiller wanted to test the effects of such particles, they did not have an established animal experiment system, so they could not directly test HPV
.

However, dairy cows and bovine papillomavirus (BPV) gave them an excellent experimental platform
.
If they can first verify the effectiveness of their ideas and methods in cattle, and then slightly modify and reproduce the strategy in HPV, then they can explore the feasibility of this vaccine in disguise
.

The experimental results obtained by the two in animals are amazing.
Insect cells modified to produce BPV L1 protein can produce virus-like particles with the same appearance and size as real BPV
.
After they injected the mixture of broken cells into rabbits, a large amount of BPV antibodies were produced in the rabbit's serum
.
These serums can not only prevent BPV from infecting experimental cells in vitro, but also can prevent infection when diluted by a million times
.

This means that an available strategy to prevent papillomavirus infection is emerging
.
Everyone has also begun to accept that virus-like particles are feasible to block virus infections
.

Dream vaccine

Of course, Lowy and Schiller's ultimate goal is to deal with HPV rather than BPV, so they need to test the effect of virus assembly on HPV
.
They initially used Hausen's original strain isolated from cervical cancer specimens as the test object
.
But the L1 protein obtained from this strain of HPV is not like BPV, which can be assembled on its own
.

They believe that because cancer cells are prone to gene mutations, and this HPV that causes cancer has acquired some genetic changes, which makes L1 unable to assemble successfully
.
In order to verify this possibility, they selected two HPV strains that are not carcinogenic and make the cervical infection benign
.
The L1 protein isolated from this strain can be assembled without the need for L2 protein
.
In fact, one amino acid difference determines that L1 of oncogenic HPV cannot fulfill this function
.

With the mass production of HPV L1 virus particles, many biological companies have begun to promote vaccine research and development
.
Lowy and Schiller and Johns Hopkins University completed the first HPV16 L1 virus particle (VLP) vaccine clinical trial
.
There were 36 participants, and all of them had a strong specific immune response
.

Afterwards, a study involving 800 volunteers also showed the good defense effect of the vaccine.
None of the vaccinated volunteers experienced persistent cervical infection caused by HPV16
.
Subsequently, the composition of the vaccine rose from HPV16 to two types of virus particles, HPV16 and HPV18
.

The two HPV vaccines were approved by the US FDA in 2006 and 2009, respectively, for the prevention of cervical precancerous lesions and cervical cancer
.
Now, we can make an appointment for the HPV vaccine to protect ourselves
.
According to Lowy and Schiller's research, only one shot can trigger a powerful protective effect
.
This may greatly protect developing countries or regions where vaccines are difficult to obtain
.

Note: The original text has been deleted

Reference materials:

[1] Harald zur Hausen – Facts.
NobelPrize.
org.
Retrieved September 1st 2021 from https:// The Nobel Prize in Physiology or Medicine 2008.
Retrieved September 1st 2021 from https:// HPV vaccines for cancer prevention.
2017Lasker~DeBakey Clinical Medical Research Award.
Retrieved September 1st 2021 from https://laskerfoundation.
org/winners/hpv-vaccines-for-cancer-prevention/