Will the Vaccine End the Pandemic? This Question Must Be Answered First

In early December, Indonesia announced an unusual plan for vaccinating its populace against COVID-19. Instead of giving vaccines to endangered groups like healthcare workers and the elderly — like virtually every other country that has released a vaccination plan — Indonesia will give the vaccines to normal, healthy adults aged 18 to 59.

The aim of the plan is to end the outbreak in Indonesia by targeting not vulnerable people but those who disproportionately transmit the virus — the hubs of the country’s social network. “Our aim is herd immunity,” said Amin Soebandrio, a biologist and director at the Eijkman Institute for Molecular Biology in Jakarta, Indonesia.

But there’s one major problem with the Indonesian plan: no one knows if the first wave of successful COVID vaccines can bring about herd immunity. Trials have shown the vaccines can prevent people from getting sick, not that they prevent people from getting infected with the virus and passing it on.

The distinction is often ignored, but some researchers say it is central in determining the long-term course of the pandemic, not just in Indonesia but around the world. Despite the often unspoken assumption that vaccines will return us to something like regular life — a deus ex medica ending to the horror story — it is not yet clear if they will have that power.

While vaccines are known as one of medicine’s most valuable tools, their function is more complicated than people often realize. At their best, vaccines can be sledgehammers that crush pathogens. Vaccines for smallpox and polio, for instance, have entirely eradicated the former and may soon finish off the latter. One key to these successes is that these vaccines provide sterilizing immunity — recipients are not infected by the viruses that cause the diseases and don’t pass it on. When a sufficiently large percentage of the population is immunized, it reaches herd immunity: the pathogen can’t find enough new hosts to keep propagating, and outbreaks peter out.

But smallpox and polio aren’t typical. More often, vaccines do not perfectly protect recipients from getting infected and transmitting the pathogen. With flu, for instance, the virus can invade the cells of some vaccine recipients, reproduce inside them without causing any symptoms, and then go on to infect other people who can get sick or even die. Instead of severing chains of transmission, vaccinated individuals can serve as links in the chain, bringing the pathogen to vulnerable hosts who haven’t been vaccinated. This scenario is common among respiratory diseases like COVID, since it’s easy for pathogens to invade our respiratory tracts and reproduce there before triggering a major immune response. 

If vaccines do not achieve sterilizing immunity, experts say it’s likely that the virus will continue circulating and we won’t see an abrupt end to the pandemic, even when a big majority of people have access to a vaccine and they agree to take it. Instead, there will probably be a gradual easing back of restrictions as transmission slows, more vulnerable people are protected by vaccination, and as we better understand and control the disease risks. “How fast we can expect to return to normalcy is difficult to say,” says Dobromir Dimitrov, a senior staff scientist at the Fred Hutchinson Cancer Research Center in Seattle. “It is also likely to vary from country to country, and even region to region. In many ways, it will be a new normal.” Researchers agree that mask-wearing and some level of social distancing will need to continue for quite some time.

Returning to the unfettered social activities we used to do routinely in the “before times” of 2019 will be a tricky and vague process — and its dynamics will depend heavily on how well vaccines prevent transmission.

“I honestly think this is the most important question, that affects daily life the most,” says Larry Corey, a virologist at Fred Hutch. Corey offered an example to illustrate the quandaries we will face next year: an office party to celebrate a colleague’s promotion. Most people have been vaccinated, but someone in the office lives with an elderly relative with a significant pre-existing health condition. The potential risk to the relative could be very different if we have a vaccine that prevents 50 percent of infections than if we have one that prevents 90 percent. “Can you have this party without feeling guilty? How are you going to decide?” Corey asks. “These are the everyday decisions we’ll have to make. It affects the behavior of people and the behavior of societies.”

Dimitrov and several other infectious-disease researchers recently posted a preprint study using a model to quantify the potential health effects of different kinds of vaccines. They found that a vaccine that prevented 90 percent of symptomatic illness and most infections could relatively easily reduce cases and deaths by 50 percent in 2021, as the vaccine is rolled out. A vaccine that prevented 90 percent of illness but did not prevent most infections would require vaccinating twice as many people to provide the same health benefit, they found.

So will the real COVID vaccines ward off the virus itself? All the trials that have been publicized so far look at how vaccines prevent symptomatic cases, but we do have some hints that they might reduce asymptomatic ones, as well. Moderna, whose mRNA-based vaccine was just granted emergency authorization by the FDA, recently announced some relevant data from its phase 3 trial. The company’s vaccine includes two shots given four weeks apart. When participants came back for the second shot, 38 subjects in the placebo group tested positive for the virus; among the vaccine group, only 14 did, suggesting a two-thirds decrease in infections. AstraZeneca, whose vaccine may have more global impact than the mRNA vaccines from Moderna and Pfizer, since it can be stored in a regular fridge and should cost only around $4, has also announced that the vaccine decreased infections, but it hasn’t released any of the data. 

Corey says the best way to understand the vaccines is to run a trial where researchers closely follow participants to watch the viral dynamics of everyone who gets infected. “You have to vaccinate people and essentially swab them every day and test the samples every day. It might end up being a million samples,” he says. He hopes to secure funding to run such a study on a college campus in the spring. Without a study like that, we could glean similar information by watching infection rates in vaccinated populations over the long term, says Corey, “but do you really want to wait until 2022 to answer this?”

In the meantime, researchers are continuing to work on dozens of other vaccine candidates that might be cheaper, more effective against infection, or superior in some other way to the first wave of vaccines. Paul Griffin, an infectious-disease expert at the University of Queensland, is helping to run trials on four vaccines, including one intriguing candidate from the company Symvivo that comes in a capsule that can be stored at room temperature and taken easily by mouth. “It’s highly likely we won’t ever find a perfect vaccine,” says Griffin. “They all have strengths and weaknesses.”