A New Age for Vaccines

Vaccines have saved countless lives, eradicated smallpox; and prevented a host of complications including paralysis, brain damage, organ failures, and birth defects. There are many different vaccines, but these are the ones that we are most familiar with:

Maryland vaccinations for school aged children (depending on age):

• Pertussis (whooping cough)—a bacterial respiratory illness that can lead to pneumonia, seizures, brain damage.
• Diphtheria—a bacterium that can result in organ damage.
• Tetanus—a bacterial infection with an 11% fatality rate. It causes muscular contractions that make it difficult to swallow and breathe.
• Polio—a relatively rare virus that can cause paralysis.
• Varicella-zoster (chicken pox)—a highly contagious virus that causes itchy, skin blisters.
• The viral diseases of Measles, Mumps and Rubella can result brain damage and Rubella can cause birth defects if contracted during pregnancy.
• Streptococcus pneumoniae and Hemophilus influenzae type b—bacteria that can cause pneumonia, meningitis, inflammation of the trachea, and a bacterial infection of the blood.
• Hepatitis B—a viral disease that causes liver damage.

A new opportunity for viral influenza:

The annual influenza vaccine protects against seasonal flu and the COVID 19 protects us from new strains of COVID 19.

Even more exciting, NIH just announced that they are using mRNA technology to develop an annual flu vaccine which would protect us from all of the 20 known flu strains. To date, scientists “guess” which flu strain will occur each year. Current vaccines protect us from up to four circulating strains of influenza, and scientists usually “guess” correctly. What vaccines can’t do is protect us from novel (e.g., transmitted from another species) or unexpected flu viruses.

The new approach (which is currently being tested and not available for humans yet) would not require “guessing” which flu strain will occur each year. More importantly, it could prevent future flu pandemics as we will be vaccinated for all 20 known subtypes (including those that occur in other species).

Another exciting development from mRNA technology.

Vaccines for travelers:

• Rotavirus—a highly infectious virus (stomach flu) which causes nausea and diarrhea (think cruise ships).
• Hepatitis A—a viral disease that causes liver inflammation.
• Rabies—a viral disease caused by contact with infected animals. If untreated, it has a 99.9% mortality rate.
• Meningococcal virus which can also be deadly.
• Cholera and Typhoid which are contracted through contaminated water or food.
• Yellow Fever—spread by the mosquito, with a 50% mortality rate.

And now, cancer:

There are two vaccines that can prevent cancer: the human papillomavirus (HPV) and Hepatitis B.

Biotech is rapidly developing vaccines to treat some cancers. Conventional vaccines boost our body’s ability to defend against foreign invaders, like bacteria and viruses. Therapeutic cancer vaccines train our body to protect itself against our own cancer cells. A vaccine is used to teach our immune system to attack a particular molecule, or antigen, whether that’s a piece of a virus or a protein that coats tumor cells.

There’s one important difference between vaccines that protect against viruses and vaccines that treat cancer. The latter are treatments not prevention. Since tumor cells are larger than viruses or bacteria, our immune systems must build a substantial army of immune cells to attack them. And, getting the immune system to attack something as large as a tumor has been a challenge. But mRNA technology enables researchers to rapidly develop new vaccines to test.

Treatment vaccines use the immune system to attack cancer cells in different ways, including:

• Keeping the cancer from returning.
• Destroying any cancer cells still in the body after conventional treatments.
• Preventing a tumor from growing or spreading.

The principle behind treatment vaccines is that cancer cells contain substances, called tumor-associated antigens, that are either not present in normal cells or are at abnormally high levels in cancer cells. Vaccines train the body to recognize these antigens, which are on the surface of cells. Treatment vaccines will help the immune system recognize and react to these antigens and destroy or remove the reproductive capability of cancer cells that contain them. Vaccines can take advantage of the immune systems’ ability to store a “memory” (in T & B cells) of antigens that must be destroyed.

Other research is attempting to inject a vaccine directly into the tumor. The hope is that that the immune system will then kill not only the tumor injection site but develop immune cells that move through the body to attack similar tumors elsewhere in the body.

To date, it is more theory than reality, because these vaccine treatments muster only weak immune responses. (Our immune system has evolved to go after viral and bacterial cells not multi-cell tumors.)

Even so, biotech companies are trialing vaccines for the following cancers: bladder, prostate, lung, myeloma, melanoma, breast, brain (unsuccessful), head & neck, pancreatic, colon, kidney, and non-Hodgkin lymphoma

Biotech companies are approaching vaccines in two ways: (a) “off-the-shelf” vaccines which target antigens that are shared across patients or (b) creating tailor-made vaccines, called “bespoke” vaccines. These bespoke vaccines are developed by sampling the patient’s cancer cells and healthy tissue. Researchers compare the DNA and RNA sequences of the healthy and cancerous samples to identify patient’s mutations they can target with a vaccine. In short, they are customized to each individual’s unique immune system and cancer.

A clear advantage of the “off the shelf” vaccines is that they can be administered relatively quickly and will be much less expensive.

On the other hand, the “bespoke” approach allows scientists to target a wider range of cancer antigens. And by targeting multiple antigens it decreases the odds that cancer cells will mutate in ways that render the vaccine ineffective. (This is a current problem with immunotherapy, cancer cells mutate brilliantly causing a particular treatment to lose its effectiveness.) Bespoke technology is a better fit for fast-mutating cancers, but it is a more time consuming approach and is likely to be very expensive.

As of today, scientists do not know if a “bespoke” or “off the shelf” approach will work better, so they often test both.

Plenty of challenges remain, from figuring out how to generate immune responses strong enough to attack solid tumors; to working out how to fit these cancer vaccines into current treatment protocols.

There are still significant hurdles to overcome:

• Cancer cells are experts in fooling and suppressing our immune system.
• Some cancer treatments (e.g., chemotherapy) weaken the immune system.
• Since cancer cells start from a person’s healthy cells, they are experts at fooling our immune system.
• Larger or more advanced tumors are hard to eliminate with only a vaccine.
• People who are sick or older often have weakened immune systems.

Cancer is a formidable enemy, and we have a long way to go, but the success of the mRNA approach and its relative speed in development is tantalizing.

The mRNA technology was advanced by scientists in their unsuccessful attempt to create a vaccine to prevent AIDS. (AIDS, to date, is the fastest mutating disease that science has encountered.) Despite its ineffectiveness for AIDS, scientists were able to use what they learned to develop the remarkably successful COVID 19 vaccine in an unprecedented short time.

This demonstrates that as long as we are learning and searching, we are getting closer to success, if not for cancer, maybe something else.

Exciting times.

Angela Rieck, a Caroline County native, received her PhD in Mathematical Psychology from the University of Maryland and worked as a scientist at Bell Labs, and other high-tech companies in New Jersey before retiring as a corporate executive. Angela and her dogs divide their time between St Michaels and Key West Florida. Her daughter lives and works in New York City.