48

On June 30, 2021, the Turkey Health Ministry announced the availability of a 3rd dose of the COVID-19 vaccine for certain categories of people (namely, medical workers and those older than 50).

The announcement says:

Third doses are recommended because after six months, the effects of antibodies produced by COVID vaccines decrease.

Third doses boost antibody levels, strengthening the immune system.

Is there scientific evidence behind this claim? I assume there must be one because it possibly affects millions of people who belong to the target age.

A general vendor-agnostic answer would be the best. However, if there exists a research which is specific for a certain vaccine type or even a vendor, I would gladly accept that, too.

2
  • 6
    Why wouldn't it? The benefit may be relatively small (or almost zero), but based on how vaccines work the claim seems to make sense.
    – Mast
    Jul 7 at 18:40
  • 6
    It almost certainly boosts antibody levels, the real question is whether it matters in terms of outcomes. So you're asking the wrong question, basically. See also skeptics.stackexchange.com/questions/51994/… Finally, which vaccine is used might also matter. Generally, the mRNA vaccines had "off the charts" responses after just 2 doses, so that's why the work even against delta variant to a good extent. The other vaccines, not so much, so boosters for those may matter more.
    – Fizz
    Jul 9 at 15:36
47

Does the third dose of a COVID-19 vaccine “boost antibody levels”?

Yes, at least in certain cases. Two published studies in patients with solid organ transplants (i.e. people who are immunocompromised) have reported that more patients have an antibody titer after a third vaccine dose compared to before the third dose, and that patients with a low-positive antibody titer before the third dose have a high-positive antibody titer after the third dose.


Here's a correspondence article published in The New England Journal of Medicine. The researchers gave a third vaccine dose to 40 patients who had solid organ transplants (all doses were the Pfizer/BioNTech vaccine). They found that the number of patients with antibodies to SARS-CoV-2 increased from 40% before the third dose to 68% four weeks after the third dose.

The prevalence of anti–SARS-CoV-2 antibodies was 0% (95% confidence interval [CI], 0 to 4; 0 of 101 patients) before the first dose, 4% (95% CI, 1 to 10; 4 of 101 patients) before the second dose, 40% (95% CI, 31 to 51; 40 of 99 patients) before the third dose, and 68% (95% CI, 58 to 77; 67 of 99 patients) 4 weeks after the third dose (Figure 1). ... All 40 patients who had been seropositive before the third dose were still seropositive 4 weeks later; their antibody titers increased from 36±12 before the third dose to 2676±350 1 month after the third dose (P<0.001).

[...]

This study showed that administration of a third dose of the BNT162b2 vaccine to solid-organ transplant recipients significantly improved the immunogenicity of the vaccine, with no cases of Covid-19 reported in any of the patients.

Here's a different study with 30 patients who had received solid organ transplants that also reported positive results (the doses were a mix of Pfizer/BioNTech, Johnson & Johnson, and Moderna; read the paper for details or see 1):

Of the 6 patients with low-positive antibody titers before the third dose, all had high-positive antibody titers after the third dose. In contrast, of the 24 patients with negative antibody titers before the third dose, only 6 (25%) had high-positive antibody titers after the third dose. Two (8%) had low-positive antibody titers, and 16 (67%) remained negative.

[...]

It is encouraging that antibody titers increased after the third dose in one third of patients who had negative antibody titers and in all patients who had low-positive antibody titers. In addition, the vaccine reactions seem acceptable, given the benefits that these vaccines can confer.

@Acccumulation had previously found a preprint that supports the same conclusion. 90 (healthy) people were given a third dose of the Oxford/AstraZeneca vaccine.

Findings: [...] 90 participants received a third dose and antibody titres were significantly higher following a third dose (FRNT50 612 [IQR 351-920]) when compared with the response 28 days after a second dose (FRNT 50 319 [IQR 176-591]. T-cell responses were also boosted after a third dose. Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose.

Interpretation: A longer delay before the second dose of ChAdOx1 nCoV-19 leads to an increased antibody titre after the second dose. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlate with high efficacy after second dose and boosts T-cell responses.

These are the only published studies I have found.


1 These are the vaccines that people received in the second study I cited.

For the first 2 doses:

During the initial vaccination, 57% of the 30 patients received 2 doses of the 162b2 vaccine (Pfizer/BioNTech), and 43% received 2 doses of the mRNA-1273 vaccine (Moderna).

For the 3rd dose:

15 patients received the Ad26.COV2.S vaccine (Johnson & Johnson/Janssen), 9 received the mRNA-1273 vaccine (Moderna), and 6 received the 162b2 vaccine (Pfizer/BioNTech).

3
  • 5
    FWIW the UK National Health Service has announced plans to offer all "vulnerable" people and everyone over 50 a double vaccination of a third booster Covid jab plus flu vaccination, starting in September. There has been comment about using a different vaccine from the first two - e.g. since most over-50s in the UK would have had two shots of Astra-Zeneca, the third shot would probably by Pfizer.
    – alephzero
    Jul 7 at 3:09
  • Note that organ transplant patients are immunosuppressed, so for them it's harder to make antibodies sciencemag.org/news/2021/06/…
    – Fizz
    Jul 9 at 18:07
  • @Fizz Yes, that is correct. In the second sentence I wrote "Two published studies in patients with solid organ transplants (i.e. people who are immunocompromised) ..." Jul 10 at 4:23
10

There's some data that suggests that a third dose increases efficacy.

90 participants received a third dose and antibody titres were significantly higher following a third dose (FRNT50 612 [IQR 351-920]) when compared with the response 28 days after a second dose (FRNT 50 319 [IQR 176-591]. T-cell responses were also boosted after a third dose. Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose.

Interpretation: A longer delay before the second dose of ChAdOx1 nCoV-19 leads to an increased antibody titre after the second dose. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlate with high efficacy after second dose and boosts T-cell responses.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3873839

This is a preprint that hasn't been peer-reviewed, so it should be taken as tentative.

Also, the vaccine has been found to be less effective with transplant patients (I assume this is because of immune suppressant drugs that typically accompany a transplant). Data suggests that a third dose of the vaccine can decrease the gap between the effectiveness of vaccines for transplant patients and the general population: https://www.sciencemag.org/news/2021/06/gives-hope-third-covid-19-vaccine-dose-can-boost-protection-organ-transplant-recipients

7

Third doses are recommended because after six months, the effects of antibodies produced by COVID vaccines decrease.

There is clear evidence that protection decreases over time, but the precise timeframe is not yet certain, and likely varies with the overall fitness of the immune system being vaccinated:

Quoting the latest survey of the Swiss National COVID-19 Science Task Force:

Recent studies have characterized the decay kinetics of SARS-CoV-2 specific B and T cell responses after vaccination or infection. They estimate that neutralizing antibody IgG titers decrease with a half-life of around 100 days, while T cell responses seem to be longer lived with a half-life or around 150 days. Although a true immunologic correlate of protection from SARS-CoV-2 infection has not yet been identified, recent studies estimate based on SARS-CoV-2 Spike specific IgG levels and efficacy of different vaccines as well as protection levels from re-infection in covalescents that 20% of the initial convalescent antibody titer seems to be necessary for 50% protection from re-infections with mild to moderate symptoms and 3% to protect by 50% from severe re-infections. After natural infection, protection from mild reinfection might last at least 8 months and protection from severe disease about 16 months. In people > 65 years, this may be shortened to 3-6 months and 10-12 months, respectively. After mRNA-vaccination, 2-4 fold higher initial neutralizing antibody titers are reached than after SARS-CoV-2 infection. In the young, this could prolong protection against mild infection to 16 months and against severe infection beyond three years. However, in the people > 70-75 years, protection against mild infection may only last for 7-10 months and against severe infection for 15-24 months. These preliminary estimates rely on several assumptions and extrapolations of existing data from other vaccines leading to substantial uncertainty. Most importantly, partial immune escape variants and variants with enhanced transmission circulating in different regions globally may become dominant in Switzerland within the next months. Protection against such variants is predicted to be significantly lower and shorter lived. [...] If prevention of severe disease remains the primary goal of the overall vaccination strategy, most individuals are unlikely to require booster doses within 18-24 months. However, people > 70-75 years and other risk populations may profit from booster immunizations within one year of primary immunization and before expected epidemiologic acceleration in winter. If the strategy is expanded to limit (variant) virus circulation in the winter months, the target of primary immunization coverage needs to be increased to >80-85% of the adult population and booster doses will likely be necessary before 2022 to maintain a sufficient level of population immunity.

That was just the executive summary. More detailed evidence, with nice graphics and references to the 19 studies used in the survey is available in the main text.

To conclude:

  • There is clear evidence that protection lessens over time. The timeframe likely varies with the strength of the original protection.
  • Offering boosters for everyone over 50 after 6 months is on the cautious side, but still likely to cause a significant increase in protection.

Effectiveness of boosters

but my question was about whether the subsequent re-vaccinations actually help improve it

They do. Quoting the same source:

In contrast to this decay of circulating antibody titers, SARS-CoV-2 specific memory B cells accumulate in frequency during the first six months after infection and continue to accumulate somatic hypermutations in their immunoglobulin loci for more potent neutralizing antibody production after restimulation [2, 7]. From these memory B cells, protective immune responses will likely be re-stimulated within 5-8 days after re-infection (or booster vaccination) as observed during single dose vaccination of COVID-19 convalescents [8].

2
  • 1
    Thank you for your answer. It seems to confirm that the antibodies decrease over time, but my question was about whether the subsequent re-vaccinations actually help improve it.
    – bytebuster
    Jul 6 at 16:08
  • 4
    That's the obvious part; B cells are always ready to resume antibody production upon restimulation - and yes, B cells are still around after that time. I have edited my answer to include sources. BTW, this is also the reason COVID vaccines are given in two doses: The maximum production of antibodies is achieved when a maximum number of B cells participate in their manufacture. Hitting an immune system with plenty of B cells therefore provides a larger antibody production that hitting a naive immune system.
    – meriton
    Jul 6 at 17:14
5

On a slightly different note to the other answers, depending on your definition of "Boost antibody levels", slightly altered booster jabs are being developed to help target the various covid variants for which other vaccines may not be so effective against (e.g. https://www.bbc.co.uk/news/uk-55976037).

This would (assuming the vaccine works as intended) increase the antibody levels in a person's body by adding a slightly different set.

3

after six months, the effects of antibodies produced by COVID vaccines decrease.

As I'm not seeing any of the other answers mention this, the 6-months thing probably comes from the Israeli preliminary data announced in June...

Vaccine effectiveness in preventing both infection and symptomatic disease fell to 64% since June 6, the Health Ministry said. At the same time the vaccine was 93% effective in preventing hospitalizations and serious illness from the coronavirus.

On the other hand, Pfizer has yet to publish more on this (than that)... but they did mention this again this month.

Pfizer did not release the full set of Israeli data on Thursday (July 8), but said it would be published soon.

On the other hand, some epidemiologists have been a bit skeptical about the claim since it comes on the backdrop of Delta strain being more transmissible... and the outbreaks in Israel have been schools which had the least vaccinated populations (as the vaccines were approved/administered later to the youngest...) And the regulatory agencies of other countries/regions haven't been too excited about 3rd booster shots:

The European Medicines Agency on Friday (July 9) said it was too early to determine whether more than the two shots that are currently required for most approved COVID-19 vaccines would be called for, saying it was confident for now that the established regimen was sufficient.

Likewise the [US] CDC was "not sold" on the idea "at this time".

As I'm looking at more news, the 6-month thing could also be in ref to this UK study published [in preprint] at end of June, but mentioned on the BMJ news...

In a preprint, published on 28 June, researchers from the University of Oxford reported that extending the interval between the first and second dose to 45 weeks resulted in higher antibody titres. They also found that a third dose given 44 to 45 weeks after the second increased antibody titres further, and that adverse events were lower after the second or third dose than after the first. [...]

For the booster (third) dose, 75 participants who had their first two doses with an interval of eight to 16 weeks were assessed. The preprint reported that antibody levels 28 days after the third dose were significantly higher than 28 days after the second dose—3746 tIgG EU and 1792 respectively.

The team also found that binding antibody titres to the beta variant “increased significantly” after the third dose, while neutralising antibody titres following the booster were higher than those after the second dose against alpha, beta, and delta variants.

In the UK, the government has said it plans to roll out a booster vaccine at the start of this autumn, in order to protect the most vulnerable ahead of winter.

(Side note, there's a separate Q here about the claim on the increased interval between the first two doses. That isn't as black-and-white as the antibody count suggests, as the cellular response was lower with increased interval.)

Another side note, Turkey appears to be following the UK example on this, which seems to have planned roughly for the same group(s) to receive the 3rd dose, over 50 etc.

At first I didn't see it mentioned in the other answers, but it seems it's the [same] study from Accumulation's answer being referenced here. And its authors were themselves a bit conservative in interpreting the results:

‘It is not known if booster jabs will be needed due to waning immunity or to augment immunity against variants of concern,’ says Associate Professor Teresa Lambe OBE, lead senior author for these studies. ‘Here we show that a third dose of ChAdOx1 nCoV-19 is well tolerated and significantly boosts the antibody response. This is very encouraging news, if we find that a third dose is needed.’

2
  • If you comment below Q to "does that matter?" – why is there no frame challenge visible to me in this A? Like which Abs, where, etc? Since the shots target extinct Wuhan-S with limited epitope number, how much cross-reactivity do these Ab represent? Is real world efficacy against post-lambda influenceable by increased anti-Wuhan-Abs? Jul 9 at 21:35
  • @LangLаngС: the frame challenge surely is there in the A in the CDC and EMA statements.
    – Fizz
    Jul 10 at 5:04

You must log in to answer this question.

Not the answer you're looking for? Browse other questions tagged .