How Will the New Strains of COVID-19 Affect Our Vaccination Plans?
The mutated strains that first arose in the U.K. and South Africa and have now spread to many countries are prompting urgent studies on the effectiveness of current vaccines to neutralize the new strains.
When the world's first Covid-19 vaccine received regulatory approval in November, it appeared that the end of the pandemic might be near. As one by one, the Pfizer/BioNTech, Moderna, AstraZeneca, and Sputnik V vaccines reported successful Phase III results, the prospect of life without lockdowns and restrictions seemed a tantalizing possibility.
But for scientists with many years' worth of experience in studying how viruses adapt over time, it remained clear that the fight against the SARS-CoV-2 virus was far from over. "The more virus circulates, the more it is likely that mutations occur," said Professor Beate Kampmann, director of the Vaccine Centre at the London School of Hygiene & Tropical Medicine. "It is inevitable that new variants will emerge."
Since the start of the pandemic, dozens of new variants of SARS-CoV-2 – containing different mutations in the viral genome sequence - have appeared as it copies itself while spreading through the human population. The majority of these mutations are inconsequential, but in recent months, some mutations have emerged in the receptor binding domain of the virus's spike protein, increasing how tightly it binds to human cells. These mutations appear to make some new strains up to 70 percent more transmissible, though estimates vary and more lab experiments are needed. Such new strains include the B.1.1.7 variant - currently the dominant strain in the UK – and the 501Y.V2 variant, which was first found in South Africa.
"I'm quite optimistic that even with these mutations, immunity is not going to suddenly fail on us."
Because so many more people are becoming infected with the SARS-CoV-2 virus as a result, vaccinologists point out that these new strains will prolong the pandemic.
"It may take longer to reach vaccine-induced herd immunity," says Deborah Fuller, professor of microbiology at the University of Washington School of Medicine. "With a more transmissible variant taking over, an even larger percentage of the population will need to get vaccinated before we can shut this pandemic down."
That is, of course, as long as the vaccinations are still highly protective. The South African variant, in particular, contains a mutation called E484K that is raising alarms among scientists. Emerging evidence indicates that this mutation allows the virus to escape from some people's immune responses, and thus could potentially weaken the effectiveness of current vaccines.
What We Know So Far
Over the past few weeks, manufacturers of the approved Covid-19 vaccines have been racing to conduct experiments, assessing whether their jabs still work well against the new variants. This process involves taking blood samples from people who have already been vaccinated and assessing whether the antibodies generated by those people can neutralize the new strains in a test tube.
Pfizer has just released results from the first of these studies, declaring that their vaccine was found to still be effective at neutralizing strains of the virus containing the N501Y mutation of the spike protein, one of the mutations present within both the UK and South African variants.
However, the study did not look at the full set of mutations contained within either of these variants. Earlier this week, academics at the Fred Hutchinson Cancer Research Center in Seattle suggested that the E484K spike protein mutation could be most problematic, publishing a study which showed that the efficacy of neutralizing antibodies against this region dropped by more than ten-fold because of the mutation.
Thankfully, this development is not expected to make vaccines useless. One of the Fred Hutch researchers, Jesse Bloom, told STAT News that he did not expect this mutation to seriously reduce vaccine efficacy, and that more harmful mutations would need to accrue over time to pose a very significant threat to vaccinations.
"I'm quite optimistic that even with these mutations, immunity is not going to suddenly fail on us," Bloom told STAT. "It might be gradually eroded, but it's not going to fail on us, at least in the short term."
While further vaccine efficacy data will emerge in the coming weeks, other vaccinologists are keen to stress this same point: At most, there will be a marginal drop in efficacy against the new variants.
"Each vaccine induces what we call polyclonal antibodies targeting multiple parts of the spike protein," said Fuller. "So if one antibody target mutates, there are other antibody targets on the spike protein that could still neutralize the virus. The vaccine platforms also induce T-cell responses that could provide a second line of defense. If some virus gets past antibodies, T-cell responses can find and eliminate infected cells before the virus does too much damage."
She estimates that if vaccine efficacy decreases, for example from 95% to 85%, against one of the new variants, the main implications will be that some individuals who might otherwise have become severely ill, may still experience mild or moderate symptoms from an infection -- but crucially, they will not end up in intensive care.
"Plug and Play" Vaccine Platforms
One of the advantages of the technologies which have been pioneered to create the Covid-19 vaccines is that they are relatively straightforward to update with a new viral sequence. The mRNA technology used in the Pfizer/BioNTech and Moderna vaccines, and the adenovirus vectors used in the Astra Zeneca and Sputnik V vaccines, are known as 'plug and play' platforms, meaning that a new form of the vaccine can be rapidly generated against any emerging variant.
"With a rapid pipeline for manufacture established, these new vaccine technologies could enable production and distribution within 1-3 months of a new variant emerging."
While the technology for the seasonal influenza vaccines is relatively inefficient, requiring scientists to grow and cultivate the new strain in the lab before vaccines can be produced - a process that takes nine months - mRNA and adenovirus-based vaccines can be updated within a matter of weeks. According to BioNTech CEO Uğur Şahin, a new version of their vaccine could be produced in six weeks.
"With a rapid pipeline for manufacture established, these new vaccine technologies could enable production and distribution within 1-3 months of a new variant emerging," says Fuller.
Fuller predicts that more new variants of the virus are almost certain to emerge within the coming months and years, potentially requiring the public to receive booster shots. This means there is one key advantage the mRNA-based vaccines have over the adenovirus technologies. mRNA vaccines only express the spike protein, while the AstraZeneca and Sputnik V vaccines use adenoviruses - common viruses most of us are exposed to - as a delivery mechanism for genes from the SARS-CoV-2 virus.
"For the adenovirus vaccines, our bodies make immune responses against both SARS-CoV-2 and the adenovirus backbone of the vaccine," says Fuller. "That means if you update the adenovirus-based vaccine with the new variant and then try to boost people, they may respond less well to the new vaccine, because they already have antibodies against the adenovirus that could block the vaccine from working. This makes mRNA vaccines more amenable to repeated use."
Regulatory Unknowns
One of the key questions remains whether regulators would require new versions of the vaccine to go through clinical trials, a hurdle which would slow down the response to emerging strains, or whether the seasonal influenza paradigm will be followed, whereby a new form of the vaccine can be released without further clinical testing.
Regulators are currently remaining tight-lipped on which process they will choose to follow, until there is more information on how vaccines respond against the new variants. "Only when such information becomes available can we start the scientific evaluation of what data would be needed to support such a change and assess what regulatory procedure would be required for that," said Rebecca Harding, communications officer for the European Medicines Agency.
The Food and Drug Administration (FDA) did not respond to requests for comment before press time.
While vaccinologists feel it is unlikely that a new complete Phase III trial would be required, some believe that because these are new technologies, regulators may well demand further safety data before approving an updated version of the vaccine.
"I would hope if we ever have to update the current vaccines, regulatory authorities will treat it like influenza," said Drew Weissman, professor of medicine at the University of Pennsylvania, who was involved in developing the mRNA technology behind the Pfizer/BioNTech and Moderna vaccines. "I would guess, at worst, they may want a new Phase 1 or 1 and 2 clinical trials."
Others suggest that rather than new trials, some bridging experiments may suffice to demonstrate that the levels of neutralizing antibodies induced by the new form of the vaccine are comparable to the previous one. "Vaccines have previously been licensed by this kind of immunogenicity data only, for example meningitis vaccines," said Kampmann.
While further mutations and strains of SARS-CoV-2 are inevitable, some scientists are concerned that the vaccine rollout strategy being employed in some countries -- of distributing a first shot to as many people as possible, and potentially delaying second shots as a result -- could encourage more new variants to emerge. Just today, the Biden administration announced its intention to release nearly all vaccine doses on hand right away, without keeping a reserve for second shots. This plan risks relying on vaccine manufacturing to ramp up quickly to keep pace if people are to receive their second shots at the right intervals.
"I am not very happy about this change as it could lead to a large number of people out there with partial immunity and this could select new mutations, and escalate the potential problem of vaccine escape."
The Biden administration's shift appears to conflict with the FDA's recent position that second doses should be given on a strict schedule, without any departure from the three- and four-week intervals established in clinical trials. Two top FDA officials said in a statement that changing the dosing schedule "is premature and not rooted solidly in the available evidence. Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19."
"I understand the argument of trying to get at least partial protection to as many people as possible, but I am concerned about the increased interval between the doses that is now being proposed," said Kampmann. "I am not very happy about this change as it could lead to a large number of people out there with partial immunity and this could select new mutations, and escalate the potential problem of vaccine escape."
But it's worth emphasizing that the virus is unlikely for now to accumulate enough harmful mutations to render the current vaccines completely ineffective.
"It will be very hard for the virus to evolve to completely evade the antibody responses the vaccines induce," said Fuller. "The parts of the virus that are targeted by vaccine-induced antibodies are essential for the virus to infect our cells. If the virus tries to mutate these parts to evade antibodies, then it could compromise its own fitness or even abort its ability to infect. To be sure, the virus is developing these mutations, but we just don't see these variants emerge because they die out."
Should We Use Technologies to Enhance Morality?
Should we welcome biomedical technologies that could enhance our ability to tell right from wrong and improve behaviors that are considered immoral such as dishonesty, prejudice and antisocial aggression?
Our moral ‘hardware’ evolved over 100,000 years ago while humans were still scratching the savannah. The perils we encountered back then were radically different from those that confront us now. To survive and flourish in the face of complex future challenges our archaic operating systems might need an upgrade – in non-traditional ways.
Morality refers to standards of right and wrong when it comes to our beliefs, behaviors, and intentions. Broadly, moral enhancement is the use of biomedical technology to improve moral functioning. This could include augmenting empathy, altruism, or moral reasoning, or curbing antisocial traits like outgroup bias and aggression.
The claims related to moral enhancement are grand and polarizing: it’s been both tendered as a solution to humanity’s existential crises and bluntly dismissed as an armchair hypothesis. So, does the concept have any purchase? The answer leans heavily on our definition and expectations.
One issue is that the debate is often carved up in dichotomies – is moral enhancement feasible or unfeasible? Permissible or impermissible? Fact or fiction? On it goes. While these gesture at imperatives, trading in absolutes blurs the realities at hand. A sensible approach must resist extremes and recognize that moral disrupters are already here.
We know that existing interventions, whether they occur unknowingly or on purpose, have the power to modify moral dispositions in ways both good and bad. For instance, neurotoxins can promote antisocial behavior. The ‘lead-crime hypothesis’ links childhood lead-exposure to impulsivity, antisocial aggression, and various other problems. Mercury has been associated with cognitive deficits, which might impair moral reasoning and judgement. It’s well documented that alcohol makes people more prone to violence.
So, what about positive drivers? Here’s where it gets more tangled.
Medicine has long treated psychiatric disorders with drugs like sedatives and antipsychotics. However, there’s short mention of morality in the Diagnostic and Statistical Manual of Mental Disorders (DSM) despite the moral merits of pharmacotherapy – these effects are implicit and indirect. Such cases are regarded as treatments rather than enhancements.
It would be dangerously myopic to assume that moral augmentation is somehow beyond reach.
Conventionally, an enhancement must go beyond what is ‘normal,’ species-typical, or medically necessary – this is known as the ‘treatment-enhancement distinction.’ But boundaries of health and disease are fluid, so whether we call a procedure ‘moral enhancement’ or ‘medical treatment’ is liable to change with shifts in social values, expert opinions, and clinical practices.
Human enhancements are already used for a range of purported benefits: caffeine, smart drugs, and other supplements to boost cognitive performance; cosmetic procedures for aesthetic reasons; and steroids and stimulants for physical advantage. More boldly, cyborgs like Moon Ribas and Neil Harbisson are pushing transpecies boundaries with new kinds of sensory perception. It would be dangerously myopic to assume that moral augmentation is somehow beyond reach.
How might it work?
One possibility for shaping moral temperaments is with neurostimulation devices. These use electrodes to deliver a low-intensity current that alters the electromagnetic activity of specific neural regions. For instance, transcranial Direct Current Stimulation (tDCS) can target parts of the brain involved in self-awareness, moral judgement, and emotional decision-making. It’s been shown to increase empathy and valued-based learning, and decrease aggression and risk-taking behavior. Many countries already use tDCS to treat pain and depression, but evidence for enhancement effects on healthy subjects is mixed.
Another suggestion is targeting neuromodulators like serotonin and dopamine. Serotonin is linked to prosocial attributes like trust, fairness, and cooperation, but low activity is thought to motivate desires for revenge and harming others. It’s not as simple as indiscriminately boosting brain chemicals though. While serotonin is amenable to SSRIs, precise levels are difficult to measure and track, and there’s no scientific consensus on the “optimum” amount or on whether such a value even exists. Fluctuations due to lifestyle factors such as diet, stress, and exercise add further complexity. Currently, more research is needed on the significance of neuromodulators and their network dynamics across the moral landscape.
There are a range of other prospects. The ‘love drugs’ oxytocin and MDMA mediate pair bonding, cooperation, and social attachment, although some studies suggest that people with high levels of oxytocin are more aggressive toward outsiders. Lithium is a mood stabilizer that has been shown to reduce aggression in prison populations; beta-blockers like propranolol and the supplement omega-3 have similar effects. Increasingly, brain-computer interfaces augur a world of brave possibilities. Such appeals are not without limitations, but they indicate some ways that external tools can positively nudge our moral sentiments.
Who needs morally enhancing?
A common worry is that enhancement technologies could be weaponized for social control by authoritarian regimes, or used like the oppressive eugenics of the early 20th century. Fortunately, the realities are far more mundane and such dystopian visions are fantastical. So, what are some actual possibilities?
Some researchers suggest that neurotechnologies could help to reactivate brain regions of those suffering from moral pathologies, including healthy people with psychopathic traits (like a lack of empathy). Another proposal is using such technology on young people with conduct problems to prevent serious disorders in adulthood.
Most of us aren’t always as ethical as we would like – given the option of ‘priming’ yourself to act in consistent accord with your higher values, would you take it?
A question is whether these kinds of interventions should be compulsory for dangerous criminals. On the other hand, a voluntary treatment for inmates wouldn’t be so different from existing incentive schemes. For instance, some U.S. jurisdictions already offer drug treatment programs in exchange for early release or instead of prison time. Then there’s the difficult question of how we should treat non-criminal but potentially harmful ‘successful’ psychopaths.
Others argue that if virtues have a genetic component, there is no technological reason why present practices of embryo screening for genetic diseases couldn’t also be used for selecting socially beneficial traits.
Perhaps the most immediate scenario is a kind of voluntary moral therapy, which would use biomedicine to facilitate ideal brain-states to augment traditional psychotherapy. Most of us aren’t always as ethical as we would like – given the option of ‘priming’ yourself to act in consistent accord with your higher values, would you take it? Approaches like neurofeedback and psychedelic-assisted therapy could prove helpful.
What are the challenges?
A general challenge is that of setting. Morality is context dependent; what’s good in one environment may be bad in another and vice versa, so we don’t want to throw out the baby with the bathwater. Of course, common sense tells us that some tendencies are more socially desirable than others: fairness, altruism, and openness are clearly preferred over aggression, dishonesty, and prejudice.
One argument is that remoulding ‘brute impulses’ via biology would not count as moral enhancement. This view claims that for an action to truly count as moral it must involve cognition – reasoning, deliberation, judgement – as a necessary part of moral behavior. Critics argue that we should be concerned more with ends rather than means, so ultimately it’s outcomes that matter most.
Another worry is that modifying one biological aspect will have adverse knock-on effects for other valuable traits. Certainly, we must be careful about the network impacts of any intervention. But all stimuli have distributed effects on the body, so it’s really a matter of weighing up the cost/benefit trade-offs as in any standard medical decision.
Is it ethical?
Our values form a big part of who we are – some bioethicists argue that altering morality would pose a threat to character and personal identity. Another claim is that moral enhancement would compromise autonomy by limiting a person’s range of choices and curbing their ‘freedom to fall.’ Any intervention must consider the potential impacts on selfhood and personal liberty, in addition to the wider social implications.
This includes the importance of social and genetic diversity, which is closely tied to considerations of fairness, equality, and opportunity. The history of psychiatry is rife with examples of systematic oppression, like ‘drapetomania’ – the spurious mental illness that was thought to cause African slaves’ desire to flee captivity. Advocates for using moral enhancement technologies to help kids with conduct problems should be mindful that they disproportionately come from low-income communities. We must ensure that any habilitative practice doesn’t perpetuate harmful prejudices by unfairly targeting marginalized people.
Human capacities are the result of environmental influences, and external conditions still coax our biology in unknown ways. Status quo bias for ‘letting nature take its course’ may actually be worse long term – failing to utilize technology for human development may do more harm than good.
Then, there are concerns that morally-enhanced persons would be vulnerable to predation by those who deliberately avoid moral therapies. This relates to what’s been dubbed the ‘bootstrapping problem’: would-be moral enhancement candidates are the types of individuals that benefit from not being morally enhanced. Imagine if every senator was asked to undergo an honesty-boosting procedure prior to entering public office – would they go willingly? Then again, perhaps a technological truth-serum wouldn’t be such a bad requisite for those in positions of stern social consequence.
Advocates argue that biomedical moral betterment would simply offer another means of pursuing the same goals as fixed social mechanisms like religion, education, and community, and non-invasive therapies like cognitive-behavior therapy and meditation. It’s even possible that technological efforts would be more effective. After all, human capacities are the result of environmental influences, and external conditions still coax our biology in unknown ways. Status quo bias for ‘letting nature take its course’ may actually be worse long term – failing to utilize technology for human development may do more harm than good. If we can safely improve ourselves in direct and deliberate ways then there’s no morally significant difference whether this happens via conventional methods or new technology.
Future prospects
Where speculation about human enhancement has led to hype and technophilia, many bioethicists urge restraint. We can be grounded in current science while anticipating feasible medium-term prospects. It’s unlikely moral enhancement heralds any metamorphic post-human utopia (or dystopia), but that doesn’t mean dismissing its transformative potential. In one sense, we should be wary of transhumanist fervour about the salvatory promise of new technology. By the same token we must resist technofear and alarmist efforts to balk social and scientific progress. Emerging methods will continue to shape morality in subtle and not-so-subtle ways – the critical steps are spotting and scaffolding these with robust ethical discussion, public engagement, and reasonable policy options. Steering a bright and judicious course requires that we pilot the possibilities of morally-disruptive technologies.
Podcast: The Friday Five - your health research roundup
The Friday Five is a new series in which Leaps.org covers five breakthroughs in research over the previous week that you may have missed.
The Friday Five is a new podcast series in which Leaps.org covers five breakthroughs in research over the previous week that you may have missed. There are plenty of controversies and ethical issues in science – and we get into many of them in our online magazine – but there’s also plenty to be excited about, and this news roundup is focused on inspiring scientific work to give you some momentum headed into the weekend.
Covered in this week's Friday Five:
- Puffer fish chemical for treating chronic pain
- Sleep study on the health benefits of waking up multiples times per night
- Best exercise regimens for reducing the risk of mortality aka living longer
- AI breakthrough in mapping protein structures with DeepMind
- Ultrasound stickers to see inside your body