Covid-19 vaccine rollouts are finally upon us. They hope that herd immunity—protection from an infectious disease that occurs once a sufficient proportion of the population has been vaccinated or infected—is on the horizon. But even though the first vaccines to receive emergency use authorisation from the US Food and Drug Administration are exceptionally effective at preventing Covid-19, data cannot yet tell us if they hinder transmission of SARS-CoV-2, the virus that causes the disease.
The question of whether immunisation prevents recipients from becoming ill and from infecting others is not unique to the current pandemic. According to Dawn Bowdish, a professor of pathology and molecular medicine at McMaster University, this so-called sterilizing immunity was a key factor in eliminating smallpox.
The smallpox, or variola, virus ravaged human populations for thousands of years, evidenced by traces of pustules found on the 3,000-year-old mummy of Egyptian pharaoh Ramses V. Reports indicate the virus was spreading globally by the first century C.E., and it eventually became a centuries-long pandemic. Historians think the disease killed more than 300 million people between 1900 and its official eradication in 1980. “Smallpox changed the history of the world-changing royal successions and the outcomes of wars that affected the destinies of whole countries,” says Natasha Crowcroft, senior technical adviser for measles and rubella at the World Health Organization.
The fight against smallpox inspired early inoculation efforts and led to English physician Edward Jenner’s cowpox vaccine against smallpox in 1796. “The [smallpox] vaccination caused sterilizing immunity, meaning that you don’t carry any of the virus. The antibodies that you generate, the responses you generate, clear the virus from your system entirely,” Bowdish says.
Although many vaccines widely used today (against measles, for example) produce very effective sterilising immunity, others, such as the hepatitis B vaccine, do not. With these vaccines, an individual’s immune system is trained to prevent illness, yet the pathogen can persist in that person’s body, potentially allowing them to infect others. A lack of sterilizing immunity means that the pathogen can continue to circulate in a population, where it may cause illness in unvaccinated and vulnerable people or evolve to evade our immune responses, Bowdish explains.
Sterilising immunity may have been a lofty goal for Covid-19 vaccine manufacturers, though not necessary to curb disease. According to Crowcroft, the very concept of such immunity is nuanced. “In reality, the spectrum of protection might best be framed as the extent to which vaccination prevents transmission of the wild-type virus or bacteria,” she says.
The case of rotavirus—which causes severe vomiting and watery diarrhoea and is especially dangerous to infants and young children—is fairly straightforward. Vaccination limits, but does not stop, the pathogen from replicating. As such, it does not protect against mild disease. By reducing an infected person’s viral load, however, it decreases transmission, providing substantial indirect protection. According to the Centers for Disease Control, four to 10 years after the 2006 introduction of a rotavirus vaccine in the US, the number of positive tests for the disease fell by as much as 74 to 90 per cent.
The pathway to vaccine-mediated control of an infectious disease is not always so direct. Ultimately, whether, and to what degree, inoculation prevents transmission depends on the pathogen itself, the host or hosts it infects and the interaction between the two, Bowdish says.
For example, vaccines against Bordetella pertussis, the primary bacterium that causes whooping cough, or pertussis, do a great job of preventing illness but do not entirely clear the pathogen. Rather, as B. pertussis replicates in the upper respiratory tract, vaccine-induced antibodies apply pressure via natural selection to weed out bacteria whose disease-causing genes are turned on. Because these same genes are responsible for the parts of the microorganisms that are targeted by antibodies, bacteria that keep them turned off evade the immune response and hang out undetected in the upper respiratory tract, Bowdish explains. This becomes a problem when someone with a naive immune system, such as an infant, contracts the pathogen. In the absence of antibodies, B. pertussis’s disease-causing genes become activated again, causing illness. Nevertheless, the introduction of pertussis vaccines in the 1940s cut annual US cases from more than 100,000 to fewer than 10,000 by 1965. In the 1980s cases began slowly climbing again as parents increasingly refused to vaccinate their children. Today there is renewed focus on reducing the chance of exposure and getting antibodies to infants by immunizing pregnant women and new mothers.
Efforts to arrest the spread of polio provide additional insight into the complexity of stopping an epidemic. The two main categories of inoculations against polioviruses confer different types of immunity. The inactivated polio vaccine (IPV) protects against systemic infection and consequent paralysis but does not stop viral replication in the gut, so it offers no indirect protection to unvaccinated individuals. The oral polio vaccine (OPV) generates localized intestinal immunity, preventing infection and protecting against disease and transmission. Because the OPV uses a weakened live poliovirus, however, in rare cases among under-immunised populations, the attenuated virus mutates, circulates and once again causes illness. The Global Polio Eradication Initiative and the World Health Organization recommend distinct vaccination strategies depending on the local context. In places where wild polio still exists, OPV is key to slowing transmission. In areas where the wild virus has been eradicated, IPV keeps populations protected. Thanks to widespread immunisation programs, the US has been polio-free since 1979, and the disease is on the verge of global eradication.
In a paper in the October 2020 issue of the American Journal of Preventive Medicine, researchers modelled what a Covid-19 vaccine with varying types of protection could mean. They found that if a vaccine protects 80 per cent of those immunized and 75 per cent of the population is vaccinated, it could largely end an epidemic without other measures such as social distancing. “Otherwise, you won’t be able to rely on the vaccine to return us to ‘normal,’” says Bruce Y. Lee, a co-author of the paper and a professor at the CUNY Graduate School of Public Health and Health Policy. That is, if the vaccine only prevents disease or reduces viral shedding rather than eliminating it, additional public health measures may still be necessary. Even so, Lee stressed that a widespread nonsterilizing vaccine could still reduce burden on the health care system and save lives.
Influenza may provide the best blueprint of what to expect going forward. The most common flu vaccine—the inactivated virus—is not “truly sterilizing because it doesn’t generate local immune response in the respiratory tract,” Crowcroft says. This fact, coupled with low immunisation rates (often shy of 50 per cent among adults) and the influenza virus’s ability to infect and move between multiple species, enables it to constantly change in ways that make it hard for our immune system to recognize. Still, depending on the year, flu vaccines have been shown to reduce hospitalizations among older adults by an estimated 40 per cent and intensive care admissions of all adults by as much as 82 per cent.
Research on seasonal coronaviruses suggests that SARS-CoV-2 could similarly evolve to evade our immune systems and vaccination efforts, though probably at a slower pace. And data remain mixed on the relationship between symptoms, viral load and infectiousness. But ample precedent points to vaccines driving successful containment of infectious diseases even when they do not provide perfectly sterilizing immunity. “Measles, diphtheria, pertussis, polio, hepatitis B—these are all epidemic-prone diseases,” Crowcroft says. “They show that we don’t need 100 per cent effectiveness at reducing transmission, or 100 per cent coverage or 100 per cent effectiveness against disease to triumph over infectious diseases.”