(FINANCIAL TIMES) - In Ohio, anyone getting a Covid vaccine could win one of five lottery prizes of US$1 million (S$1.3 million). New Jersey residents getting the jab are offered free beer. One site in New York boasted an even more unlikely incentive: a courtesy marijuana joint.
Since the start of the year, America has successfully ramped up its vaccine campaign so that over 160 million people have had at least one shot so far - already meeting the target President Joe Biden had set for July 4.
But if children are included, that is still less than half of the population and in some parts of the country the take-up of vaccines has started to slow. As a result, states and businesses are turning to unorthodox incentives to try to persuade the vaccine-hesitant to have a jab.
The United Kingdom, one of the other countries with a relatively advanced vaccine programme, is facing some similar problems.
Even though hesitancy has fallen as vaccines have been rolled out, take-up is uneven: The majority of the 23 people in hospital in Bolton, north-west England, where the highly transmissible variant first found in India is spreading, had been eligible for vaccination. Only five had been vaccinated.
When the news broke at the end of last year that coronavirus vaccines could be more than 90 per cent effective, it seemed to usher in the prospect of eradicating the disease.
But over the past couple of months, those heady hopes have given way to a more complicated reality. For governments, the appearance of new variants and the persistent hesitancy over vaccines are causing problems for their plans to reopen economies and bring some normality back to life. For the scientists tracking the pandemic, they have called into question the idea that societies will ever achieve herd immunity, even when there is an abundant supply of vaccines.
Herd immunity is the concept that an infectious disease can be eradicated once a sufficient threshold of immunity has been reached - either through already having had the infection or through vaccination. Once that level is passed, so the theory goes, transmission of the virus slows rapidly and it eventually fizzles out.
At the start of the pandemic, some scientists hoped the threshold could be as low as 60 per cent. For most of the last year, Mr Peter Hale, executive director of the Foundation for Vaccine Research in Washington, says the United States' health agencies have informally set herd immunity at about 75 per cent.
The trial results for the messenger ribonucleic acid (mRNA) vaccines developed by BioNTech/Pfizer and Moderna seemed to hold the prospect of getting over that hurdle, he says. But given that the B.1.1.7 variant, which was first reported in the UK and is now dominant in the US, is more transmissible than the strains prevalent in the country last year, the threshold for herd immunity may now be closer to 80 per cent, he says.
In the UK, the potential spread of the variant first identified in India, which is thought to be even more transmissible, further complicates the country's calculations about herd immunity.
The result is that if the vaccine-hesitant cannot be persuaded to change their minds and if new variants of the virus continue to spread, many countries will struggle to stamp out Covid-19. Instead, they will remain vulnerable to surges that could require new restrictions.
Director of the University of Texas' Covid-19 modelling consortium, Professor Lauren Ancel Meyers, says estimates of the proportion of the population that would need to be vaccinated to achieve herd immunity range from 60 per cent to 80 per cent.
"I would not say that herd immunity is out of the question," she says. "But I would say that herd immunity is pretty unlikely in the foreseeable future, in most communities and in most cities in the US and across the world."
Viral and human behaviour
The estimates about herd immunity vary so widely because they depend on two unpredictable factors: how the virus behaves and how humans behave. Scientists do not know the extent to which new variants will make the virus more transmissible, nor how many people will get the vaccine.
Dr Natalie Dean, a biostatistician at the University of Florida, says the calculations can often be crude, assuming we are "gas particles bouncing around", rather than humans with different patterns of contact, with some potential superspreaders.
Throwing vaccines into the mix creates more variables. In the Seychelles, the virus has burst back on to the island despite a high level of vaccination. Some researchers believe this could be because it was relying on a shot from Chinese pharma company Sinopharm, which some studies have shown may be about 50 per cent effective, despite reporting a better efficacy rate in its clinical trial.
Researchers also do not know how effective the shots are at preventing transmission, although early studies suggest they do limit the ability of vaccinated people to pass along the virus. It is also not clear if they will stand up to variants that emerge in the future.
No 'on-off switch'
Scientists prefer to think about herd immunity as a cumulative process, rather than a finish line to cross.
Professor John Edmunds, a professor at the London School of Hygiene and Tropical Medicine, says it is not an "on-off switch". The higher the level of immunity in a population, the more it will slow the virus down, he says.
"Eventually, there will be such high levels of immunity in the population that the virus will struggle to spread even without any social restrictions. We are still quite a long way from this point, unfortunately," he says.
If an area achieves true herd immunity, even cases introduced from outside will fail to spread. Professor Jonathan Ball, a professor of virology at the University of Nottingham, gives measles as an example where we only see outbreaks when the local immunity drops below a certain threshold.
"If you have a small amount of infected people every year coming into the UK with measles, but most of the population is immunised, it simply won't take off," he says.
Professor Paul Hunter, professor of medicine at the University of East Anglia, sees "a lot of misunderstanding about what herd immunity means, even among medical people. They confuse reduced transmission through vaccination with true herd immunity".
Prof Hunter doubts whether herd immunity for the Sars-CoV-2 virus can be achieved with any of the current jabs, given levels of hesitancy and incomplete protection provided by even the best vaccines, which is likely to wane over time.
Misuse of the term
"For me, there are two reasons why misusing the term 'herd immunity' may be damaging," he says. "The first is that some individuals may think wrongly that they don't need to be vaccinated because they are protected by everyone around them who has been vaccinated. The second is that people are using herd immunity as an argument for relaxing social distancing restrictions too quickly."
If - as now - large swathes of the world remain unvaccinated, travel between regions risks setting off new outbreaks in areas where vaccine uptake has been erratic and importing variants that can evade vaccination.
"Cities can serve as reservoirs where the virus can continue to thrive and continue to evolve, and we would very likely see variants emerging and spreading around the globe," Prof Meyers says.
In the US, public health experts believe incentives like free beer - or making vaccination a condition of employment or going to school - may lure the "vaccine indifferent" to get a jab.
Dr Jennifer Reich, author of Calling The Shots: Why Parents Reject Vaccines, says the first priority will be encouraging these people who are not intentionally opposed to vaccines, but nor are they motivated to seek one out.
But after this category, it gets trickier. There are several groups of people who are vaccine-hesitant, sceptical or even entrenched anti-vaxxers. In the US, they range from Trump supporters who have long played down the severity of the pandemic, to more nonconformist left-wingers who scorn anything "unnatural".
Vaccine resistance is not limited to the US. A survey of 14 countries found about six in 10 people were willing to take a vaccine, with France, Singapore and Japan among the least willing, according to the Imperial and YouGov poll between November and February.
More recently, concerns about a rare side effect from the Oxford/AstraZeneca vaccine have hit confidence: After the shot was suspended in March, the number of people who perceived it was safe dropped substantially in France, Germany, Italy and Spain, according to YouGov.
Across the Western world, minority ethnic groups are often more sceptical of the vaccine after a history of scarring experiences with the medical establishment.
In the US, black and Hispanic adults have been the most likely to say that they will "wait and see" before they get vaccinated themselves, according to data from the Kaiser Family Foundation.
Income also has an influence: Knowing someone who has been vaccinated is an important factor in people's acceptance, and earlier in the year, households earning over US$90,000 were almost twice as likely to know people who had been vaccinated than those with incomes of less than US$40,000.
Vaccine hesitancy is falling in the UK but it is still significant in the black, Asian and minority ethnic populations. Some 66 per cent of white people say they would take the vaccine when invited, compared with 55 per cent of black respondents, in an April survey by the Vaccine Confidence Project.
Recent headlines about side effects - even if they are very rare - have weighed on vaccine acceptance. Dr Alex De Figueiredo, a research fellow at a project run at the London School of Hygiene and Tropical Medicine, says the most common reasons for being unsure about whether to vaccinate were overall safety concerns and the rare blood-clotting side effect in the AstraZeneca vaccine in particular. But he adds that having a choice in vaccines increases confidence, so the UK's decision to allow under-40s a choice of shot should boost uptake.
Even without concerns about side effects that regulators say are more prevalent in the young, there may be a higher degree of hesitancy in this group because they are less likely to become seriously ill. "The challenge of that right now is that we have inadvertently communicated to young people that they might not really have to worry about this," Dr Reich says.
Individual v collective benefits
Part of the problem may be that Covid-19 vaccines have been sold for their benefits to individuals, rather than as a collective good, she adds. Young people, more likely to be asymptomatic carriers, may have a higher probability of infecting others.
The BioNTech/Pfizer vaccine is now approved in the US for children over 12, giving the potential of vaccinating more of the population. However, experts expect many parents to be hesitant because they will see it as an more of an individual risk/benefit calculation and know far fewer children have become seriously ill with Covid-19.
"We're already facing the battle among adults and I think we may be facing an even greater battle when it comes to vaccinating children," says Prof Meyers.
Populations in developing countries tend to be more convinced of the benefits of vaccination, so when they receive more supplies, their citizens may be more likely to take it.
A pre-pandemic survey of 149 countries from 2015 to 2019 published in the medical journal The Lancet found respondents in Africa, Latin America and many parts of Asia were more likely to believe that vaccines were safe and effective. There are exceptions, including Brazil, where a vaccine-sceptical leader has led to greater reluctance among some of the population.
Dr Kate O'Brien, the World Health Organisation's director of immunisation, vaccines and biologicals, says there has been some hesitancy influenced by the regulatory and policy decisions in Europe, but overall there was no "significant stepping back" from the desire to have the vaccine in countries receiving shots from the WHO programme Covax.
People in low- and middle-income countries "know how horrible infectious diseases can be", says Prof Ball.
Though the debate continues over how to increase supplies to the developing world, he adds that "it is ironic that people who can't get access to vaccines are the ones most likely to take them".