KUALA LUMPUR: With new Covid-19 variants emerging amid easing pandemic restrictions, some are concerned about waning immunity and have called for a second vaccine booster dose (fourth jab) to increase protection levels.
Experts and the public, however, are divided on the need for a second booster, a debate that re-emerged following the United States (US) Centers for Disease Control and Prevention (CDC) and Food and Drug Administration's (FDA) recent approval of a fourth round of Covid shots.
Epidemiologist Professor Datuk Dr Awang Bulgiba Awang Mahmud of Universiti Malaya said the CDC and FDA's recommendation for those above 50 to get a fourth dose appeared rushed.
"In a country where many people are resisting even getting the primary series, this is a bit surprising.
"I am not surprised at the recommendations for the immunocompromised as it has been shown that they probably require three doses as their primary series, so a fourth dose is simply their first booster," he told the New Straits Times.
CDC director Dr Rochelle P. Walensky, in a statement on March 29 said people over the age of 50 could get an additional booster four months after their prior dose to increase their protection further.
"This is especially important for those 65 and older and those 50 and older with underlying medical conditions that increase their risk for severe disease from Covid-19 as they are the most likely to benefit from receiving an additional booster dose at this time," Walensky said.
The FDA on March 29 authorised a second booster dose of either the Pfizer or the Moderna Covid-19 vaccines for older people and certain immunocompromised individuals.
Besides the US, the European Medicines Agency had on April 6 recommended fourth doses for the immunocompromised and those aged 80 and above while the United Kingdom in February recommended it for the immunocompromised and those aged 75 and above.
On March 24, Singapore's multi-ministry task force tackling the coronavirus had accepted the recommendation by the Expert Committee on Covid-19 Vaccination that everyone aged 80 and above, those living in aged care facilities, and medically vulnerable people should receive a second booster dose from about five months after receiving their first booster dose.
Dr Awang Bulgiba, who is also the Science, Technology and Innovation Ministry's Covid-19 Epidemiological Analysis and Strategies Task Force chairman said at present, immunocompromised individuals and the elderly might benefit from a fourth dose although the length of protection is still uncertain.
"Mandatory fourth doses (second boosters for this targeted group) should only be considered if there is clear evidence that it is necessary and clearly explained to those who require it."
Health Minister Khairy Jamaluddin today said individuals aged 60 and above with comorbidities would be given an option to get their second booster shots some four to six months after their first booster dose.
Khairy had said the elderly over 60 without comorbidities could also opt for the shot but only on the advice of a medical professional.
The decision, Khairy said was made after the Technical Working Group reviewed scientific studies as well as Malaysian cohort studies showing that individuals aged 60 and above with comorbidities such as lung disease, heart disease, kidney disease, liver disease and diabetes are at higher risk of serious symptoms and death from Covid-19.
Dr Awang Bulgiba noted that while Covid-19 vaccines were effective at providing a little extra protection from infection - including against the dominant Omicron variant - endless boosting might not be practical or a viable strategy nor is it how these vaccines were meant to be used.
He said that existing scientific evidence suggests limited indications for a fourth dose.
"It seems that the protection afforded by boosters is simply by sheer levels of circulating antibodies rather than via an Omicron-specific version of the vaccine.
"This is not a sustainable public health strategy as we cannot keep administering boosters every six months or so or every time a new variant crops up. The advent of the XE and other variants, for example, do not warrant boosters unless evidence emerges that these variants are more virulent than their predecessors.
"Not only will repeat boosting be costly, but it is unclear whether this will prove detrimental to the immune system."
Dr Awang Bulgiba said a recent publication (not peer-reviewed) had found that the T-cell response after a booster remains robust, which offers hope that a fourth dose is not yet necessary for most people.
"T-cell immunity protects against severe disease. Thus, although the Omicron variant may be able to evade some antibodies, robust T-cell immunity can help the body fight off the Omicron variant in vaccinated persons."
He, therefore, said people under 50 years old should get their first booster (third dose) and not rush into the second booster as the fourth dose should be kept as a reserve strategy in case a more virulent variant emerges.
The general population, he said should also continue with non-pharmaceutical interventions (NPI) such as mask-wearing, physical distancing and sanitisation to protect against symptomatic infection.
"Boosting with a fourth dose now when infection rates are declining does not make public health sense.
"Masks need to be worn properly and at all times except while dining. If possible, the public should opt for N95/KN95/KF94/FFP2 masks or better. If not, then double-masking is a cheaper alternative – an inner surgical mask with an outer good-fitting washable cloth mask."
The World Health Organisation, in a statement on Jan 11, warned that "a vaccination strategy based on repeated booster doses of the original vaccine composition is unlikely to be appropriate or sustainable."
Molecular virologist Dr Vinod Balasubramaniam, a senior lecturer in microbiology at the Jeffrey Cheah School of Medicine and Health Sciences of Monash University Malaysia said second booster shots should only be made available to this specific targeted group.
There were absolutely no benefits to an added boost for people who do not need one (like younger individuals without any health issues), especially when it comes to building the longer-lasting cellular immunity that helps to protect the body from severe disease, he said.
"What is our goal with vaccinations? Is it just to prevent all infections, which is almost impossible, or is it to prevent severe disease and hospitalisations and death, which is a much more reasonable goal? I believe we have probably reached that in most individuals with three doses.
"Besides, this is the same vaccine formulation that we have been getting all along - Pfizer-BioNTech, Moderna, AstraZeneca, and Johnson & Johnson Covid jabs.
"While we do probably get some additional protection, it does not offer great additional protection as what we got from the first, second and third doses. We simply can't boost our way out of the pandemic. It's not feasible."
Universiti Sains Malaysia virologist Dr Muhammad Amir Yunus said a fourth shot could be offered as an option for the elderly and immunocompromised, particularly those without any history of severe side effects from Covid-19 vaccines.
"This could come as mandatory should there be an emergency such as if the country records a high death rate or a sharp increase in severe cases that might potentially burden our healthcare system."
Dr Muhammad Amir said it is, however, too early to consider a fourth shot for the general healthy population as data showed that there was only a slight increase in terms of cellular response (which might still be well-maintained by the third shot) except for those who received Sinovac as their primary series.
Why did CDC and FDA approve the second booster
The US health authorities' decision was based on data from Israel that suggested a second booster dose administered at least four months after the first booster could reduce the risk of hospitalisation and death in adults 60 and older and other high-risk individuals, Dr Vinod shared.
This decision, he said acknowledged the increased risk of severe disease in certain populations including those who are elderly or over the age of 50 with multiple underlying conditions, along with the currently available data on vaccine and booster effectiveness.
"The science behind this is that when a person gets vaccinated, they have a surge in antibodies, which could prevent a Covid-19 infection from taking hold but over time, those antibodies (first layer of defence) would start to wane.
"Even with booster shots, the evidence indicates that the boost in antibodies is only temporary, but that does not mean a person is fully vulnerable to the coronavirus if they contract it again. Their body still has memory cells that can recognise Covid-19 and start to produce antibodies. That process may not happen quickly enough to prevent an infection.
"But it should, for most people, be able to prevent their symptoms from becoming severe that they wind up in the hospital (this is true for majority of the people who have received their primary doses and first booster shot).
"However, for the elderly and immunocompromised, there is a stronger case for trying to keep antibody levels high because they tend not to see as strong of an immune response from vaccination."
An Israeli study found that a fourth Covid shot (Pfizer boosters) halves death risk among severe patients over 60. The Times of Israel on April 10 reported that the study, which has not yet been peer-reviewed, also found that fourth shots halve the odds that a patient will need ventilation.
The study's author Dr Tal Brosh was quoted as saying that the findings suggested that fresh booster for each new Covid-19 wave may be wise.
Another study published in the New England Journal of Medicine on April 5, titled 'Protection by a Fourth Dose of BNT162b2 against Omicron in Israel' found that rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 (Pfizer) vaccine than after only three doses.
Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period, the paper noted.
Israel began administering a fourth dose of Pfizer vaccine to persons 60 years of age or older on Jan 2.
Have we developed natural immunity against Covid and the many variants
Dr Awang Bulgiba said natural immunity occurred in people who have been infected but whether it is long-lasting is another matter.
"There is evidence to suggest that reinfection could occur in previously infected persons.
"Whether cross-neutralisation occurs with natural infection is not clear but some evidence suggested that vaccinated and boosted persons could develop broad cross-neutralising antibodies against many variants.
"However, we really should not be looking at antibodies alone. Cellular immunity is perhaps more important here as the protection tends to be longer-lasting and is against severe disease and death rather than against symptomatic infection."
How long after Covid can a person get the fourth jab
If someone has had a third dose (first booster) and then was infected with Covid-19, then there is no rush to get a fourth dose as it is likely that the antibody levels will remain elevated for a few months and more importantly, the cellular immunity has been shown to last much longer than that, Dr Awang Bulgiba explained.
Can second booster take a mix-and-match approach?
Dr Awang Bulgiba said studies in Israel have used messenger RNA (mRNA) vaccines (Pfizer or Moderna) for fourth doses, hence boosters should continue along that line.
Sinovac is not recommended as a booster due to its low efficacy, Dr Muhammad Amir said, adding that Sinovac recipients should receive other vaccines as a booster.
Potential side effects from second booster
Currently, both the approved Pfizer and Moderna vaccines have a solid safety record, and serious side effects were rare, Dr Vinod said.
The risk of myocarditis (one of these uncommon side effects) in the 50-plus age range, he said was considered to be minimal.
"The side effect profile that was looked at in a million individuals who had received additional doses in the Israel study looks very favourable in this age range.
"However, there are temporary, side effects after the shot. Fatigue, fever, headache, muscle pain, chills and nausea are all common symptoms reported after the Covid-19 booster."
Dr Muhammad Amir said while most people might not have any abnormal reaction, a certain percentage of population might react to the vaccines differently.
"Detailed investigation should follow if there are any adverse events following immunisation (AEFI) reported, for instance, whether it is due to vaccine itself or perhaps due to the component in the vaccines, handling, or needles condition.
"Unfortunately, almost all of us don't know if we will have severe reaction (not any typical reaction) before taking the vaccine. People who experience these side effects should always follow up with medical practitioners to monitor the condition."
Why isn't there an Omicron specific vaccine?
Data on the real-world effectiveness of vaccines made clear that three doses of current mRNA vaccines (Pfizer and Moderna) could largely restore high levels of protection from Omicron, particularly from severe disease, hospitalisation, and death, Dr Vinod shared.
Dr Vinod further said preliminary animal studies have cast doubt on whether Omicron-specific vaccines, which are designed to match critical mutations in the variant, will provide better protection.
"In a small primate study released not long ago, the Omicron-specific booster did not offer significantly better protection from omicron than a current vaccine. The study only involved eight monkeys, but the findings were consistent with several other studies in mice, which all suggest that a single variant-specific booster will not offer ultimate protection against a new variant.
"Vaccine makers are now looking for a bivalent vaccine combining both the Omicron and the original ancestral strain to move forward."
Dr Awang Bulgiba said what was of concern is not just SARS-CoV2 which causes Covid-19 but the possibility of other coronaviruses or other viruses emerging in the future.
"In the case of coronaviruses, work has begun on pan-coronaviruses vaccines which produce cross-neutralising antibodies (that can protect against most or all variants)."
Pfizer Chief Executive Albert Bourla had on Wednesday said that the company could possibly develop a new vaccine that protects against the Omicron variant as well as older forms of Covid-19 before the end of 2022.
Bourla said the firm was also working on producing a vaccine that could provide good protection for a whole year, meaning people would come back annually for boosters, as with influenza shots.