KUALA LUMPUR, July 19 – The Covid-19 vaccine is really a three-dose primary regimen to get a sufficient immune response, not two doses, says an infectious disease epidemiologist from Yale University.
Prof Dr Sten H. Vermund, who is a dean at the Yale School of Public Health in the United States, pointed out that with waning immunity from Covid-19 vaccination and the emergence of new variants, the notion of “fully vaccinated” status comprising two vaccine doses was no longer applicable.
“I think it was a mistake to think of Covid-19 vaccination as two doses. It was never two doses,” Dr Vermund told CodeBlue in a recent interview here.
“The third dose was essential to have a reasonable response. I’m not even sure we should call it a booster.”
Dr Vermund cited the three-dose Hepatitis B vaccine as an example, saying that the three doses comprise the primary series to get 95 per cent effectiveness or higher in the general population.
In Malaysia, the hexavalent combination vaccine – which protects against six diseases, including Hepatitis B – is given under the National Immunisation Programme to children as three doses at age two, three, and five months respectively, with a booster shot given at the 18th month.
“That’s the way I think about Covid-19 – the three doses are essential for just about everyone to have a reasonable immune response to Covid-19 and the boosters are really the fourth dose, and maybe a future fifth dose and maybe a future sixth dose,” Dr Vermund said.
“Having a net of four doses – three minimum, four doses is prudent – and should be national policy.”
The Yale public health professor said there is still no research yet on how frequently Covid boosters would have to be administered, noting that different scientists have mooted booster shots every six months, annually, or every three years.
“We’ll get the kind of information after the fourth jab to see if this lasts for a couple of years, and the decline in antibody levels is not as severe as when you only had two or three jabs, or whether in fact it does wane more quickly and we need, say, yearly jabs.”
Like other countries, Malaysia considers two doses as complete Covid-19 vaccination. Earlier this year, Health Minister Khairy Jamaluddin abandoned plans to revoke access to public premises via vaccine passes for senior citizens aged 60 and above and adult recipients of two Sinovac doses who do not get a third jab.
According to the CovidNow site, 68.5 per cent of adults aged 18 and above in Malaysia have received a third dose, labelled as “first booster”. Coverage of third doses is slightly higher among seniors aged 60 and above at 70.6 per cent.
On the fourth dose, Dr Vermund recommended first priority for those aged 50 and older, as Covid-19 vaccination should be prioritised for vulnerable subgroups.
“Once you have them vaccinated, and you have enough vaccines to go around, there’s no harm to boost the immune status of younger people.”
He cited public health benefits in giving a fourth Covid jab to young adults without underlying health conditions to prevent them from inadvertently infecting vulnerable groups like the children and the elderly, even as he acknowledged that young and healthy people are less likely to fall seriously sick from Covid-19.
“So there may be a public health argument for additional doses on top of the clinical benefit argument.”
Only about 3 per cent of the elderly aged 60 and above in Malaysia have received their fourth Covid jab, or “second booster”.
Khairy told a press conference last week that the Technical Working Group (TWG) is considering a fourth Covid vaccine dose for healthy adults aged 60 years and below, likely a step-down approach to expand to individuals in their 50s first.
The Ministry of Health (MOH) currently recommends a fourth Covid vaccine shot, or a second booster, for the elderly, adults who are immunocompromised, and frontline workers.
Malaysia’s national Covid-19 immunisation programme utilised a basket of vaccines, with Pfizer-BioNTech’s mRNA vaccine comprising about 61 per cent of shots administered, followed by Sinovac’s inactivated jab at 30 per cent, AstraZeneca-Oxford at 8 per cent, and CanSino’s single-shot vaccine at 0.3 per cent.
Dr Vermund noted that the mRNA vaccine appears to have a competitive advantage, adding that future studies are needed to see if inactivated vaccines are equally robust against the Delta and Omicron variants.
He said that he had published a paper in the Nature medical journal suggesting that two doses of the inactivated vaccine with an mRNA booster in heterologous or mix-and-match inoculation, could be as effective as two mRNA doses.
“So there might be some benefit with the more immunogenic vaccines used in conjunction with cheaper and more accessible vaccines.”
When asked if recipients of inactivated vaccines should receive five jabs then, Dr Vermund said research has yet to be conducted on the efficacy of five Covid-19 vaccine doses.
“We have studies of two doses, then mRNA – that looks very potent.”
No Vaccine Prevents Infection, Vaccines Reduce Disease Severity And Transmissibility
Dr Vermund clarified misperceptions about the inability of coronavirus vaccines in preventing infection, saying that all existing vaccines against various diseases actually permit infection, but the main purpose of vaccination is to reduce the severity and transmission of infection.
On Covid-19, he cited research that shows vaccination reduces one’s viral load when infected with the coronavirus and, as such, makes it less likely for the infected person to infect other people.
“I think it’s exceedingly unlikely at the end of the day that a fully immunised individual is going to be equally transmissible in virus to others,” Dr Vermund said, adding that contagiousness could be reduced even further by wearing face masks.
He stressed that all vaccines are “infection-permissive”, including jabs against measles or Hepatitis B that do not prevent infection, but are able to protect the infected from falling ill and to prevent transmission of the virus to other people. Hence, outbreaks are prevented.
Children or adults who are fully vaccinated against measles or Hepatitis B will show a rise in antibody levels during an outbreak if their blood is tested, he pointed out.
“That means you were infected, but you will never get sick,” Dr Vermund said.
“All vaccines are infection-permissive. It’s a fundamental misunderstanding of how vaccines work.”
The American infectious disease expert, who has been working in infectious disease epidemiology for 40 years, explained that vaccines work by alerting the immune system about a threatening antigen and by empowering memory T cells to recognise that pathogen subsequently.
When someone gets infected years later after vaccination and the actual pathogen, not the antigen from the vaccine, appears in the body, memory T cells remember and recognise the pathogen and alert B cells to transform into plasma cells to start producing antibodies against the antigen from the bug.
“So it hasn’t done much to prevent the infection. It has simply permitted the immune system to mount a vigorous and rapid immune response to the infection and if it’s vigorous enough and rapid enough, you don’t get sick.”
He explained that vaccination may reduce symptomatic infection rates, saying: “For example, the virus attacks and it’s quickly dismissed so it doesn’t have a systemic infection.
“But I can tell you there has been some local infection, just that your immune system blocked it out and nipped it in the bud.”
Dr Vermund said scientists have yet to achieve “sterilising immunity” for any vaccine, including a HIV vaccine that has been worked on for 40 years but has yet to achieve sterilising immunity to completely block infection.
“When the virus gets into your body, within a half hour, it can occupy distant immunologic sites that are not as susceptible to immune surveillance, such as lymph nodes, and you can get infected very quickly,” said Dr Vermund, referring to HIV that causes AIDS.
“So we would love to have a vaccine that’s so efficient, that as soon as the virus enters the bloodstream, immediately it’s neutralised and you never establish a real infection.”
Achieving sterilising immunity, said Dr Vermund, requires a vaccine with both a B cell response that generates antibodies and a T cell response generating a cellular response; a cellular response works faster than an antibody response.
“Most of our vaccines work through B cell mediation. For cellular response vaccines, we still have a long way to go.”
