Elderly will be hardest group to protect with vaccine

The elderly are at greatest risk of dying from COVID-19, worldwide data has shown, and are among the most difficult sections of the population to protect with vaccines. But the elevated risk of infection and inflammation make it challenging to include the elderly in vaccine trials, researchers say.

Because the immune system naturally weakens with age, “vaccine manufacturers, by and large, will not use an elderly population for phase I [trials] because they want to show that it’s safe and they want to show that it’s efficacious,” John Nicholls, clinical professor of pathology at the University of Hong Kong and coronavirus expert, told University World News.

An analysis of 26 studies from around the world by researchers at Dartmouth College in the United States published last month found that the risk of dying from COVID-19 rises substantially from 0.4% for individuals aged 55 to 15% for those aged 85.

Ageing weakens the immune system making the body more vulnerable to infectious diseases, and intensifies inflammation when infections do occur. The ageing human body also loses the ability to acquire immunity through infection or vaccination, meaning that vaccines effective in younger adults may not protect people over 55.

“You basically run out of naïve immune cells that react to a pathogen the body has never seen before,” said Nicholls.

Vaccine manufacturers may have too much to lose by trialling vaccine candidates on vulnerable populations too soon. “They need to produce a vaccine and they’re not going to try it out on a 55- to 70-year-old population because there’s definitely less chance of getting an immune reaction and an immune response,” said Nicholls.

According to Nicholls, matters are worse for SARS-CoV-2, the coronavirus that causes COVID-19, because it enters human cells through a gateway protein that usually triggers inflammation, which is already elevated in the elderly.

“The body’s defence mechanism goes into overdrive. That’s why you get this nasty reaction [with COVID-19] of diffuse lung damage,” said Nicholls.

Trials that include the elderly

Experts agree that not enough has been done to find out how the elderly could respond to vaccines, even at the preclinical stage.

Phase I clinical trials test a vaccine candidate for safety and adverse reactions, usually with around 100 participants. The elderly are often left out of clinical trials. “They have comorbidities and there’s more of a chance that they’ll have adverse reactions,” Nicholls said.

Two of the vaccine candidate frontrunners, one being developed by the University of Oxford with UK-based pharmaceutical company AstraZeneca, and the other by US biotech giant Moderna, have enrolled adults over age 55 in their trials.

The Oxford programme, which includes older adults in Phase II and Phase III trials but excludes them from Phase I, was paused for a week in September in Phase III after a participant experienced inflammation on both sides of one section of the spinal cord. It has not been confirmed whether the event was due to the vaccine.

So far, Moderna is the only manufacturer to have tested their candidate vaccine on 20 adults aged over 55 in Phase I clinical trials and did so after demonstrating safety in adults aged 18-55.

Risky population groups

Phaik Yeong Cheah, an associate professor at the University of Oxford and head of the department of bioethics and engagement at the Bangkok-based Mahidol Oxford Tropical Medicine Research Unit, explained: “Studies get their inclusion and exclusion criteria to be as representative as possible of the population that they want to use the eventual drug or vaccine on, but they also have to narrow it down quite a bit because they don’t want to include people who are risky and prone to side effects.”

Cheah highlighted the “persistent challenge” of companies not recruiting participants from high-risk groups for clinical trials. “If somebody gets really ill and dies, then you’ll kill the new drug [or vaccine]. So there’s no incentive to try it,” she said.

High-risk populations, in addition to the elderly, include young children, pregnant women and those with comorbidities – more than one disease present in a person at the same time.

The downside is that when there is a vaccine, it is only valid for the population groups that participated in the clinical trials, Cheah added.

Fears over Guillain-Barré syndrome – a rare attack on the nerves by a person’s own immune system that can paralyse the body – discouraged many people from taking up the influenza vaccine, which may have exacerbated the 2009 H1N1 flu pandemic. Research, including an eight-year study in Taiwan of individuals over 50, has yet to prove an association between the influenza vaccine and the syndrome.

Transmission in the elderly

Nicholls said the types of COVID-19 vaccine currently undergoing trials will reduce cases of severe pneumonia but will not stop transmission, so vaccinated individuals exposed to the virus could transmit it to members of high-risk populations, while themselves being protected from developing the disease. “That’s why the vaccine has to be put in together with social distancing,” he said.

A vaccine delivered via a nasal spray – already used for some existing influenza vaccines – would cause the immune system to produce a type of antibody that stays in the nasal passages and intercepts viruses entering through the nose, preventing transmission.

Teams in the United States, Canada and the Netherlands are working on nasal vaccines for COVID-19, but a higher risk of severe inflammation from these vaccines, which are a live attenuated virus, discourages most manufacturers. A live attenuated vaccine is the “live [virus] but it’s basically been tampered with. People are worried that if it’s not attenuated enough, then it may end up causing disease,” said Nicholls.

“The good news is that, in the elderly, you can try to boost your immune system,” Nicholls said.

A recent review by immunologists at the universities of Palermo and Molise in Italy, King’s College London in the UK, and Harvard University in the US, highlighted evidence that suggested probiotics, micronutrients – such as zinc and vitamin E – and several chemicals in some foods – such as resveratrol in red wine and omega-3 fatty acids in fish oils could give more protection, either by stimulating the immune response and-or lowering inflammation, though these effects will vary with different people.