04/01/2022
Question:
What is the rationale for COVID-19 vaccine booster doses?
Take home messages
* Immunity against SARS-CoV-2 infection wanes 4-5 months following a 2-dose COVID-19 vaccine schedule
* Although protection against severe disease is relatively preserved following two doses, boosters provide effective additional protection against SARS-CoV-2 infection and may further improve protection against severe outcomes in older adults.
* Boosters will be particularly important to reduce transmission and impact of the Omicron variant.
* A COVID-19 booster (Pfizer or Moderna) is currently recommended for all adults who completed their primary vaccination course 5 or more months ago.
*Vaccine equity remains a global challenge; ongoing advocacy for action at a government level as well as individual contributions have potential to improve this.
Background:
The COVID-19 vaccination rollout has progressed steadily in Australia since the first doses were administered in March 2021. As of this week, 80% of Western Australians >12yo have received two doses. With a clear roadmap laid out to reopen borders in February 2022, maximizing community immunity through vaccination will be vital to limit the impact of SARS-CoV-2.
With the initial advent of COVID-19 vaccinations, the duration of vaccine-induced immunity was uncertain. With the emergence of the Omicron variant, and subsequent rapid global spread, there has been increased focus on waning immunity and the role of booster vaccinations.
Paper:
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 - October 04, 2021
Findings:
In this retrospective cohort study from California, electronic health records of almost 5 million individuals, including over 1 million individuals vaccinated with BNT162b2 (Pfizer), were reviewed. Both SARS-CoV-2 infection (positive PCR test) and COVID-19 hospitalisation were assessed as outcomes from December 14th, 2020, to August 8th, 2021.
Overall vaccine effectiveness during the study period was 73% (95% CI 72-74%) against infection.
Following vaccination withBNT162b2, effectiveness against infection fell over time from 88% (95% CI 86-89%) in the first month following vaccination to 47% (95% CI 43-51) after 5 months.
Of 5000 samples with genetic sequencing data available, the observed reduction in effectiveness over time with delta was similar to that seen with other variants, indicating that waning immunity, rather than variant immune escape was the primary driver of reduced vaccine effectiveness.
Importantly, vaccine protection against hospitalisation (overall 90% (95% CI 89-92%)) was sustained to 6 months following a two-dose schedule across age groups.
Discussion:
These findings are consistent with a number of other studies from the US and internationally showing waning protection against SARS-CoV-2 infection 5-6 months following primary vaccination.
In these studies, vaccine protection against severe COVID-19 was well preserved to at least 6 months, although waning of protection against severe disease has been observed in those >60yoin data from Israel.
1) Are booster vaccines effective?
In short, yes - observational data demonstrate good protection against SARS-CoV-2 infection following a third dose of BNT162b2 (Pfizer). Furthermore, data from Israel suggest a reduction in mortality in those aged >50y.owho received a booster compared to those who had received a two-dose primary schedule only. A booster dose of BNT162b2 was approved in the US following consideration of data from a randomised trial of 10,000 adults >16yo who received either a BNT162b2 booster of placebo. Vaccine efficacy of the booster against symptomatic infection was 95% overall.
Regarding other combinations, atrial of different booster vaccines from the UK (lead by PMH alumni Alisdair Munro) examined a range of booster doses in participants in the UK who initially received either two BNT162b2 or two ChAdOx1 (AstraZeneca) doses. Excellent antibody and cellular immune responses were observed with both mRNA booster vaccines (mRNA1273 (Moderna) and BNT162b2 (Pfizer)) with similar responses observed in those who initially received ChAdOx1 and BNT162b2 courses. This is promising in the Australian context where both mRNA boosters are now available for all adults who received their second dose more than 5 months ago.
2) How does the Omicron variant impact on need for boosters?
The Omicron variant has raised great concern due to both its rapid spread and the possession of a large number of mutations with potential to confer immune "escape" thereby reducing protection from previous vaccination or infection. Early lab studies have shown that antibodies from previous immunisation have markedly reduced ability to neutralise the omicron variant. Notably, reduced antibody neutralisation reflects one aspect of immunity against SARS-CoV-2, and previous data suggests that the broad-ranging T-cell immune response following vaccination may be better preserved with new variants, providing ongoing protection against severe disease.
With ongoing spread through the UK (amongst many countries),epidemiological data suggest that vaccine induced immunity against infection is significantly reduced with Omicron. Promisingly, boosters appear to increase efficacy to ~75% against symptomatic infection in early estimates. Emerging laboratory data support the protective effect of boosters, with studies showing a 30-60 fold increase in neutralising antibody levels against the Omicron variant following a booster. It also appears that there is a broadening of the antibody response following a third dose, providing more cross-protection against Omicron. Extrapolating from data during the circulation of the delta variant, it may follow that breakthrough infections following a booster dose will also result in lower viral loads, potentially attenuating onward transmission.
All considered, it appears that boosters will be very important in protecting against the spread of Omicron at a community level, as well as providing additional individual protection, particularly in those at higher risk of severe disease. In Western Australia, booster doses for those eligible prior to the borders opening, together with ongoing efforts to reach those who remain unvaccinated, will be very important in limiting the impact when COVID-19 arrives in our state.
3) What about vaccine equity?
The ready availability of booster doses in Australia, the US and other high-income countries stands in stark contrast to the paucity of vaccines in low-income settings, particularly in many countries on the African continent. Aside from the obvious ethical considerations, a global effort to address vaccine inequity will be essential to conquer the COVID-19 pandemic. The path to addressing inequity will require coordinated international action, including increased vaccine delivery through commitment to the COVAX facility and other pathways. Locally, there has been advocacy for the Australian government to increase its commitment to this global effort recognising the important role that we can play in the Asia Pacific region particularly.
On an individual level, forgoing a booster shot is unlikely to impact vaccine inequity but, but there are avenues to help including through a donation to the UNICEF Vaccinaid initiative.
4) Will we need further boosters beyond three doses?
At this stage it is uncertain whether further booster doses will be required beyond a third dose. The necessity, optimal timing and make up of any further booster regimens will be informed by further studies of longitudinal immunity and immune protection following three doses. Ongoing viral evolution has potential to influence this space as well.
Source - Dr Daniel Yeoh, Infectious Diseases Physician
Perth Children's Hospital
