Vaccines Don't Need to Be Limited to Infectious Diseases

I’m told that a character in Israel Zangwill’s novel Children of the Ghetto asks, rhetorically, if someone whose views he dislikes couldn’t be vaccinated “against free-thinking." Zangwill’s book appeared in 1892. Vaccine development was in its infancy. More than a century later, vaccines have become a cornerstone of public health. They teach our immune systems to recognize and fight off invading bacteria or viruses.

When the COVID-19 pandemic erupted, most of us were happy to be assured that a vaccine would get life back to normal. It didn’t quite. Still, vaccines have been vital in saving lives and controlling the pandemic. Isn’t that what vaccines are for: to protect us against infectious diseases?

In Zangwill’s imagination, "vaccination" suggested something far beyond that. Could science actually be heading toward that imaginary place?

Unconventional vaccines

Towards the end of the 20th century, immunologists saw that the immune system could be mobilized against "intruders" other than infectious pathogens. By the 1990s, they were trying to develop vaccines against complex and socially costly conditions: obesity, addiction, dementia, and cancer. Some projects, including the search for an anti-obesity vaccine, have struggled. Others have got further. However, the going has been tough.

Addiction vaccines

Addictive substances, such as cocaine and heroin, don’t nudge the immune system into action. Researchers set about chemically modifying their molecular structures so that they do. The substances they developed became known as addiction vaccines.

Success with human volunteers has been modest. There have been no large clinical trials, but research continues. Despite researchers’ optimistic claims, future progress is hard to predict. Nor is it clear how the vaccines would be used.

Mental health professionals generally assume that the vaccines would be used therapeutically, alongside existing drugs and counseling. Their principal use would be in preventing relapse among people undergoing treatment.

Twenty years ago, the suggestion was made that addiction vaccines could, and perhaps should be used preventatively, rather than therapeutically. In 1997, a leading addiction researcher pointed out that once the cocaine vaccine had been shown to be safe and to work, the question of whom to vaccinate would become unavoidable. Identifying "risk groups" for preventative vaccination would be ethically and constitutionally problematic. Who, then? Vaccinating the whole population would alleviate the risk of discrimination, but would it be acceptable?

Alzheimer’s disease vaccines

Since the 1990s, scientists have been trying to mobilize the immune system against Alzheimer’s disease. Some "immunotherapies" target the "plaques," and some the "tangles" characteristic of the condition.

The path to a cure is strewn with obstacles, and clinical trials have shown limited benefit. Here, too, the dilemma of when and whom to immunize arises. Part of the problem is that patients with advanced-stage dementia are typically older individuals. Older people generally have weakened immune systems, either from co-morbidities or simply from an age-related decline in immune function. Could vaccines be more effective if used earlier: in preventing Alzheimer’s rather than in treating it?

The possibility of serious adverse reactions is very real. Overreaction to immunotherapy could actually make things worse for the patient. Despite the millions of dollars spent on research and all the articles published, there’s still little evidence of clinical benefit and no licensed vaccine.

Cancer vaccines

The surfaces of some cancer cells differ from those of corresponding normal cells. If the immune system could be taught to target a cancer cell’s distinctive surface, vaccines might be possible.

The idea of cancer immunotherapy, mobilizing the immune system in cancer treatment, has its roots in the 19th century. There has been major progress since the 1990s, and today some cancer therapies already combine immunotherapy with chemotherapy and/or hormone therapy and surgery. Here, too, there’s no definitive answer to the question of how best to integrate immunotherapy with other treatments. And here, too, oncologists acknowledge the risk of triggering an autoimmune response in some patients. Such a reaction would mean that the immune system would mistakenly attack normal cells.

In all, major questions of "when" and "for whom" still remain. If vaccines do little for patients with established carcinomas, maybe they’d be more effective at an earlier stage, or even used preventatively.

mRNA: a game-changer?

Prior to the COVID-19 pandemic, few people had heard of messenger ribonucleic acid (mRNA). That has surely changed.

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The scientists who developed the successful mRNA COVID-19 vaccines had been trying to develop cancer treatments. The pandemic led them to refocus their work. Now that the mRNA technology has been shown to work, their hope is that it will prove an equally powerful tool in fighting cancer. Might an mRNA cancer vaccine become available by the end of the decade? Some experts think so.

Invaluable, but not a holy grail

At the start of the COVID-19 pandemic, questions of access, equity, and possible refusal of vaccines were set aside. "Vaccination" has come to stand for the protection of each of us individually and of society at large. However, the step from protecting against infectious pathogens to protecting against Alzheimer’s disease, addiction, cancer, or obesity is a very large one. Thirty or more years of research have led to very limited clinical benefit. Major questions regarding how best to use any such vaccines remain unanswered (or even avoided). When to immunize? Whom to immunize? How to guard against potentially devastating side effects?

Let’s hope the mRNA technology will, indeed, prove a game-changer. We shouldn’t expect too much too soon. But we should learn from the pandemic and start discussing these "what then?" questions.