Coronavirus vaccines can reduce disease severity and fatality, but the emergence of new strains has raised questions about their effectiveness and future vaccination strategy. Some vaccine makers are rolling out variant-specific boosters to head off the Omicron surge, while others are developing pan-coronavirus vaccines that will hopefully offer protection against all variants.
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Yet, only some countries have access to vaccine technology and supply. Using a global database, infectious disease experts in Asia and Latin America conducted a review of more than 50 real-world studies, which found that current booster shots are effective in preventing severe disease and death.
For the review, data was selected from VIEW-hub, an online, interactive, map-based platform for visualising the most recent data on vaccine use and impact, including more than 330 studies on vaccine effectiveness. It was developed by Johns Hopkins Bloomberg School of Public Health and the International Vaccine Access Center.
Dr Anna Ong-Lim, professor at the University of Philippines College of Medicine and a member of the technical advisory group of the Department of Health there, said the review shows all current vaccines are highly effective in preventing severe disease and death in the general population (84.2%) and the elderly (87.4%).
"It is reassuring because as I mentioned, one of the limitations in lower and middle-income countries is that we have to work with whatever vaccines are available in our system and there might be a perception that some vaccines are better than others," she told a media roundtable.
While efficacy is an outcome in a clinical trial necessary for getting approval from regulators, effectiveness is how it works in the real world, and is determined by several factors, including population groups, vaccine platforms and schedules. Vaccine effectiveness refers to the reduction percentage of potential severe outcomes.
Dr Ong-Lim said the review shows that three-dose homologous (same) and heterologous (mixed) vaccine schedules are effective in preventing severe disease and death. All homologous vaccines are in the same range of 75% to over 90% of effectiveness, while all heterologous vaccines are in the range of 80% to 98%.
From top left, Dr Anna Ong-Lim, Dr Julian Chan, Dr Suwat Chariyalertsak, Dr Bruce Mungall, Dr Christopher Lee and Dr Rontgene Solante.
When it comes to the duration of vaccine effectiveness, Dr Ong-Lim said the level of protection against symptomatic infection wanes in three months after booster vaccination from 67% to around 30%. But for severe disease and death, the level of protection is "impressive", dropping slightly from 87.5% to 77.5%.
When asked about the fourth dose, Dr Ong-Lim said "there is not a great deal of data on its effectiveness" in the global database, but we have seen "an encouraging effect of protection" against severe disease mainly in the elderly because they are the most vulnerable group offered the fourth dose.
To help fill the gap is a new finding from Thailand. Using data in Chiang Mai, infectious disease experts studied the effectiveness of three-dose and four-dose heterologous vaccine schedules in preventing severe disease and death at the peak of Omicron transmission from Feb-April. People received a variety of vaccines, such as inactivated, viral vector and mRNA.
Dr Suwat Chariyalertsak, dean of the Faculty of Public Health at Chiang Mai University, said the study shows the third dose (the first booster) can provide a similar level of protection for adults (85%) and elderly (89%-94%). When it comes to the fourth dose (the second booster), there are no cases of severe disease and death.
Dr Suwat said the study compared the effectiveness of the third dose of each vaccine brand, which yields a similar level of protection of around 90%.
"We don't see any outcomes in people who get the fourth dose, but it is around 80% for those who don't [get] any vaccines," he said.
In conclusion, the fourth dose of all vaccines can boost protection. Vaccine coverage "may be a much stronger predictor of protection against severe outcome" rather than platforms and schedules. Booster programmes should incorporate different vaccines according to local supply and logistics.
"Elderly people and those who have comorbid [conditions] should get booster shots, either three doses or four doses, to prevent severe outcomes and keep hospital facilities for others," he said.
Still, some have raised doubts over mixed schedules. Dr Bruce Mungall, Asia medical director of vaccines and infectious diseases at AstraZeneca, said large safety studies have been conducted into adverse events for multiple vaccines. As data comes through, the potential risk is lower with additional doses.
"But importantly, what becomes very obvious is health risks associated with Covid-19 infection are much worse," he said. "If we can prevent Covid-19 from happening through vaccination, we can also prevent these risks entirely."
This could be the largest global vaccination campaign, he added. So far, over 12 billion doses have been administered globally, saving almost 20 million lives.
Dr Christopher Lee, adjunct professor at Taylor's School of Medicine in Malaysia, said these results have shown that national vaccination campaigns can use current vaccines to boost protection.
Many countries in the region have mixed schedules for pragmatic and logistical reasons.
"It is important to remind ourselves as some countries have already got variant-specific vaccines, especially those in the West, but for most of us in this part of the world, our turn may take quite a bit of time. It is important not to delay vaccination. Use what we have," he said.
Variant-specific booster shots are being rolled out across the US and Europe to tackle currently circulating Omicron variants. Made by Pfizer and Moderna, these bivalent vaccines include two pieces of mRNA that allow human cells to produce the spike protein of the original strain and subvariants.
Dr Lee said even though vaccine effectiveness in preventing infection wanes three months after the booster, the level of protection against severe disease remains and can be improved by the fourth dose. Maintaining the level of immunity will likely require boosting annually or every four-to-six months for the vulnerable population.
"The second booster is something on the cards. In many countries, including Malaysia, those older than 60 and those with comorbidity are being offered the second booster," he said.
He attributed the lower uptake of the second booster in his country to pandemic fatigue and safety concerns. To address hesitancy, he stressed that it is important to educate the public about vaccination. When more information comes through, a regimen will follow.
"I am sure people in many countries are complaining they need a third, fourth and fifth shot. That kind of question will come up. Very likely, with more data in the future, we can come up with a regimen, perhaps something like influenza. Yearly or twice yearly. I think it is probably moving in that direction," he said.
- The expert review of more than 50 real-world studies was published in Research Square on Sept 6. Access it at researchsquare.com/article/rs-2015733/v1.
- The study of three-dose and four-dose heterologous vaccine schedules was published in Research Square on Aug 26. Access it at researchsquare.com/article/rs-1973470/v1.