What about a third (booster) Pfizer vaccine dose?

18 November 2021


By Dr Mark Thomas, Associate Professor in Infectious Diseases, University of Auckland

At a time when the collective attention of Aotearoa New Zealand is largely focussed on delivering two doses of the Pfizer vaccine to as many people as possible, along comes another issue seeking our attention. How much benefit will be achieved by giving a third dose of the Pfizer vaccine to those people who had their first two doses some months ago? This question is prompted by accumulating evidence that: (i) vaccine efficacy wanes in the months following vaccination, and (ii) vaccine efficacy is less against the Delta variant than against previous variants. (1)


Figure 1. A study of 3.4 million people receiving care from Kaiser Permanente Southern California showed that vaccine (Pfizer) effectiveness against infection declined from 88% in the first month after the second dose to less than 60 percent in all age groups five months later (A). However, vaccine effectiveness against hospital admission remained consistently high: 93 percent for Delta and 95 percent for other variants (B). (1)

Very similar results have been found in other studies. An analysis of UK data by Public Health England found that for the Pfizer vaccine, efficacy against infection declined from approximately 90 percent at 14 days after the second dose to approximately 70 percent approximately 120 days later. (Figure 2A) In contrast, vaccine efficacy against hospitalisation (Figure 2B), and against death (Figure 2C) remained above 90 percent throughout. (2)


Figure 2. Vaccine (Pfizer) efficacy in England against infection (A), hospitalisation (B), and death (C) in relation to days following the second vaccine dose. (2)

In contrast a recently published report from the US estimated that vaccine efficacy against COVID-19 hospitalisation following two doses of the Pfizer vaccine was 91 percent (95 percent confidence intervals: 88-93 percent) at 14-120 days after the second vaccine dose, but was only 77 percent (95 percent CIs: 67-84 percent) at >120 days after the second vaccine dose. (3)

There are a few studies that can provide useful information about the potential benefits of a booster dose of the Pfizer vaccine. A two-slide presentation, with almost no text, presented at the Pfizer Second Quarter 2021 Earnings Teleconference on 28 July 2021, summarised the effect of a third Pfizer vaccine dose on serum neutralising antibody titres in a very small number of adults. (4) One slide showed that in 11 adults aged 18-55 years the serum neutralising antibody titres were more than five times higher one month after the third dose than they had been one month after the second dose. It also showed an even greater increase in serum neutralising antibody titres in 12 adults aged 65-85 years. In these older adults the one-month post third dose serum neutralising antibody titres were more than 11 times higher than the one month post second dose titres. (Figure 3)

Figure 3. The coloured bars represent the ability of serum from vaccinees, when diluted to very low concentrations, to neutralise SARS-CoV-2 viruses preventing them from infecting cells. Note that the vertical axis has a logarithmic scale. At one month after the second vaccine dose the serum from 11 vaccinees aged 18-55 years could, on average, be diluted to one in 310, and still retain the ability to neutralise early human (wild type = WT) SARS-CoV-2 viruses. The same serum samples were slightly less effective at neutralising Delta variant viruses. They could, on average, be diluted to one in 241, and still neutralise Delta variant SARS-CoV-2 viruses. At one month after a third vaccine dose the serum from 11 vaccinees could be diluted to one in 1547 (on average) and still neutralise wild type viruses, or to one in 1321 and still neutralise DELTA variant viruses. (4)

An article recently published in the New England Journal of Medicine reports on the effect of administration of a booster Pfizer vaccine dose in people in Israel, aged more than 60 years, who had completed their initial vaccine course approximately six months previously. 


Figure 4. The figure (from “world in data - covid”) shows the successive waves of the SARS-CoV-2 epidemic in Israel from 12 March 2020 to 30 October 2021. The green arrows represent the two doses of the primary vaccination course given 21 days apart, in January-March 2021, and the third single booster dose, given in August 2021. 

In response to a large epidemic wave that began in November 2020, the Israeli government delivered a vaccination programme that administered two doses of the Pfizer vaccine to more than 50 percent of the population by the end of March 2021. However, the emergence of the Delta variant and waning vaccine immunity was followed by another large epidemic wave that began in August 2021. In response to this surge in cases the Israeli government approved the delivery of a third dose of the Pfizer vaccine (identical to those used for the two primary vaccinations) for high-risk people and those aged more than 60 years. 

The incidence of symptomatic SARS-CoV-2 infection, and of severe COVID-19 disease (defined as resting respiratory rate >30/min, or oxygen saturation <94% while breathing air) was studied in people who had received two vaccine doses before 1 March 2021, and who had, or had not, received a booster vaccine dose between 30 July 2021 and 31 August 2021. The incidence of infection, and of severe COVID-19 was studied for the same 32 day period (30 July 2021 - 31 August 2021). Thus, the effect of the booster dose could not be determined for durations greater than 32 days. Approximately 700,000 study subjects received the booster dose and approximately 400,000 did not. (5) 

SARS- CoV-2 infection occurred in 4,439 (of approximately 400,000) people who had not received a booster, and in 934 (of approximately 700,000) people who had received a booster. The rate of infection was 11.3 times lower in the boosted people than in the non-boosted people. Delivering a booster dose to 1,000 people reduced the number who developed infection from approximately 26 to approximately 2.6. The number needed to be vaccinated to prevent one infection was approximately 40.

Severe COVID-19 occurred in 294 (of approximately 400,000) people who had not received a booster, and in 29 (of approximately 700,000) people who had received a booster. The rate of severe disease was 19.5 times lower in the boosted people than in the non-boosted people. Delivering a booster dose to 1000 people reduced the number who developed severe COVID-19 from approximately two to approximately 0.14. The number needed to be vaccinated to prevent one case of severe disease was approximately 500.

Vaccine efficacy against infection, which was estimated to have fallen to approximately 50 percent at 6-7 months after the primary vaccine course, was estimated to again be approximately 95 percent by 12-20 days after the booster dose. The article provided no information on either the numbers of cases requiring hospitalisation or on deaths. 

A very recent press release from Pfizer, in mid-October, reported that a third vaccine dose, given approximately 11 months after administration of the second dose, reduced by 95 percent, the chance of having symptomatic SARS-CoV-2 infection. Symptomatic SARS-CoV-2 infection occurred in 109 people, out of approximately 5,000 who received a placebo third dose, but in only five people, out of approximately 5,000 who received a Pfizer vaccine third dose. (6) The number needed to be vaccinated to prevent one infection was approximately 50. Unfortunately the Pfizer press release provided no information about the impact of the booster dose on rates of severe covid-19, hospitalisation or death. The manuscript of the article that reports on this study is not yet available.

In summary, there is clear evidence that a booster dose of the Pfizer vaccine does increase serum neutralising antibody titres, and also reverses the decline in vaccine efficacy against infection, which occurs in the months following administration of the second vaccine dose. However, there is also good evidence that despite vaccine efficacy against infection waning significantly in the months after the primary vaccination course, vaccine efficacy against hospitalisation and against death remains extremely high. 

The possible benefits from a booster vaccine dose will differ markedly depending on the individual’s risk of severe disease, hospitalisation, and death, and on the potential consequences of infection. People at particularly high risk of severe disease, or death, such as those over the age of 80 years, and those with severe underlying conditions, may derive benefit from a booster dose, but the duration of this benefit is unknown at present. People who, if infected, might transmit infection to a person at particularly high risk of severe disease may also be suitable candidates for a booster dose, but the same uncertainty about duration of benefit also applies to them. We need more detailed data. However, the greatest need at present is clear, to deliver a primary vaccination course to all those who wish to receive it.
 

 

References

  1. Tartof SY, et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet 2021;398:1407-16.
  2. Public Health England. Duration of protection of covid-19 vaccines against clinical disease. SAGE 9 September 2021. 
  3. Self WH, et al. Comparative effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson& Johnson) vaccines in preventing COVID-19 hospitalisations among adults without immunocompromising conditions – United States, March – August 2021. Morbidity and Mortality Weekly Report 2021;70(38):1337-43.
  4. Anonymous. COVID-19 vaccine: 3rd dose strongly boosts neutralizing titres against Delta strain. Pfizer Second Quarter 2021 Earnings Teleconference. 28 July 2021. At: https://investors.pfizer.com/events-and-presentations/event-details/2021/Pfizer-Quarterly-Corporate-Performance--Second-Quarter-2021/default.aspx
  5. Bar-On YM,  et al. Protection of BNT162b2 vaccine booster against Covid-19 in Israel. New England Journal of Medicine 2021;385:1393-400.
  6. Howard J. Booster dose of Pfizer/Biontech coronavirus vaccine shows 95.6% efficacy in Phase 3 trial, companies say. CNN. 21 October 2021. At: https://edition.cnn.com/2021/10/21/health/pfizer-booster-dose-efficacy-wellness-bn/index.html