In South Africa, people who received their first shot of the Pfizer Covid-19 vaccine must wait six weeks before returning for the second jab.

This follows updated guidance issued by the national Health Department a month ago, in light of new data showing a longer delay between doses could offer more protection.

By last week, Pfizer was the most numerous brand of vaccine being rolled out in South Africa — with just over 1.5 million people having received their first shot. On Thursday, 300,000 Johnson & Johnson jabs arrived and this week Aspen Pharmacare will release an additional one million doses.

This follows delays in getting Johnson & Johnson vaccines into the country, with some consignments declared unusable because of low production standards. This has led to growing pressure for South Africa to get greater value from the remaining vaccines in its arsenal.

What is the evidence behind the three-week extension between doses, what does this mean for your follow-up appointment and how could it help alleviate the pressure on the country’s vaccine supply?

What changed? 

The Pfizer vaccine was designed as a two-dose shot. The manufacturer recommended that the jabs be spaced three weeks apart.

When the vaccine was being tested in a clinical trial, the doses were administered with this three-week interval. This means the trials result — of 95% efficacy in preventing disease — only applied when the injections were used in this way.

In a statement issued in March, Pfizer re-emphasised that its vaccine had not been studied using an extended dosing interval despite some governments deciding to recommend a different time gap for the shots.

In light of restricted vaccine supplies and growing evidence to support the efficacy of a longer interval between doses, South Africa has opted to double the waiting time. This way, the country is able to give as many people as possible first doses as quickly as possible so they get at least partial protection from Covid-19.

In a notice shared on 19 May by the Department of Health director-general Sandile Buthelezi, the extended vaccine time frame was attributed to “emerging evidence to support a 42-day interval between the first and second doses”.

This also followed a recommendation from the ministerial advisory committee on Covid-19 vaccines that the gap be extended in the event of a shortage of doses. 

The new time frame applies to everyone who has received a first shot. So, even if one was vaccinated before 19 May (the day on which the circular was issued), the follow-up appointment will be three weeks later. People who were told to return for a second dose after 21 days will receive an electronic vaccination data system (EVDS) SMS notification about the new timing.

Messages with appointment dates for second doses are sent out three days in advance.

The short notice period allows for more vaccination sites to become operational, meaning people can be allocated to places requiring less travel time, explains Milani Wolmarans, acting chief operating officer in the Department of Health.

South Africa began Phase 2 of its national vaccine roll-out on 17 May, so 28 June is the date the first people will return to be fully immunised by Pfizer.

A gamble that paid off: Why some countries changed policy without science

Despite the vaccine only being formally tested with a 21-day gap between doses, some countries decided to deviate from this plan.

Although not as extreme as some other countries in its approach, the US Centers for Disease Control and Prevention (CDC) has made allowance for doses to be given a maximum of 42 days apart. This aligns with the updated guidance from South Africa.

Given the limited evidence available, the CDC recommends that the doses be given “as close to the recommended interval of three weeks as possible”. But when it is not possible for someone to receive their second dose within 21 days, the guidance allows for a delay of up to six weeks.

On the other hand, in December last year the UK began giving people their second Pfizer jab after 84 days. There was no data to back up any change in the Pfizer interval at that time.

The chief executives of the UK’s National Health Service (NHS) gave this explanation in a December 2020 letter to NHS staff: “Prioritising the first doses of vaccine for as many people as possible on the priority list will protect the greatest number of at risk people overall in the shortest possible time and will have the greatest impact on reducing mortality, severe disease and hospitalisations and in protecting the NHS and equivalent health services.”

Six months later, Northern Ireland, a constituent of the UK, recommended the two jabs be given a maximum of eight weeks apart, instead of 12 weeks. The country’s health department said the recommendation to shorten the dosing interval was a move to help protect more people from the virus, especially in light of rising infections caused by the Delta variant.

The UK was not alone in its decision. Canada, similarly, opted to delay the roll-out of second doses so that more people could get their first dose while more vaccines were on the way. Canada’s national advisory committee on immunisation recommended the dosing interval be extended to four months between shots.

What does the research say?

A May preprint study was the first research to directly compare the strength of people’s immune responses after receiving the second dose of Pfizer after three weeks (21 days) and after 12 weeks (84 days).

Participants on the extended dosing interval had a much stronger immune response than those on the standard three-week interval. Those who got their jabs 12 weeks apart had more than triple (3.5 times) as many antibodies in their blood than those who were immunised three weeks apart. Antibodies are proteins that help the body fight harmful pathogens such as viruses.

The small study included 172 participants, all over the age of 80. 

Ninety-nine participants got their second jab at three weeks, while the remaining 73 received theirs 12 weeks later. 

An earlier paper, published in Plos Biology in April, found that delaying the second dose of the Pfizer vaccine to 12 weeks prevented more hospitalisations and deaths when compared with the three-week interval.

Although the paper points out that when compared with Moderna — the other mRNA Covid vaccine — a shorter delay of between six to 12 weeks between Pfizer doses can yield greater results in terms of reducing hospitalisations and deaths.

This finding, however, relies on how long immunity lasts after the first dose. 

The researchers studied two hypothetical scenarios, one in which immunity drops before the second dose, and one in which it doesn’t.

In the best-case scenario, where immunity doesn’t wane before the second dose, there were fewer infections, hospitalisations and deaths. In the worst-case scenario, the benefit of delaying the second dose was far lower since fewer infections, hospitalisations and deaths were prevented. 

The decrease in hospitalisations and deaths is based on the assumption that every day 30 people are being vaccinated for every 10,000 people in the population. The researchers argue that, as immunisation programmes speed up and more people get the jab each day, the same reduction of deaths and hospitalisation is achieved with a shorter interval.

Similar mathematical modelling done in Canada in an April preprint study compared dosing intervals of three and four months to a baseline of six weeks between jabs. The paper found that, by extending the time between shots by up to four months, there was a greater reduction in severe disease.

Ultimately, the projections showed that for older people (those above 75) the ideal gap between doses was 16 weeks (four months). A longer time frame of six months was actually able to offer more protection for people between the ages of 20 and 74.

This paper echoed the Plos Biology study in that it also found it was more beneficial to extend the gap between doses when there was limited access to vaccines, because it allowed for more people to be at least partially immunised over a shorter period of time. DM/MC

This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.