Immune Responses After Vaccination With Primary 2-Dose ChAdOx1 Plus a Booster of BNT162b2 or Vaccination With Primary 2-Dose BNT162b2 Plus a Booster of BNT162b2 and the Occurrence of Omicron Breakthrough Infection
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Abstract
Background
Before the omicron era, health care workers were usually vaccinated with either the
primary 2-dose ChAdOx1 nCoV-19 (Oxford-AstraZeneca) series plus a booster dose of
BNT162b2 (Pfizer-BioNTech) (CCB group) or the primary 2-dose BNT162b2 series plus
a booster dose of BNT162b2 (BBB group) in Korea.
Methods
The two groups were compared using quantification of the surrogate virus neutralization
test for wild type severe acute respiratory syndrome coronavirus 2 (SVNT-WT), the
omicron variant (SVNT-O), spike-specific IgG, and interferon-gamma (IFN-γ), as well
as the omicron breakthrough infection cases.
Results
There were 113 participants enrolled in the CCB group and 51 enrolled in the BBB group.
Before and after booster vaccination, the median SVNT-WT and SVNT-O values were lower
in the CCB (SVNT-WT [before-after]: 72.02–97.61%, SVNT-O: 15.18–42.29%) group than
in the BBB group (SVNT-WT: 89.19–98.11%, SVNT-O: 23.58–68.56%; all
P < 0.001). Although the median IgG concentrations were different between the CCB and
BBB groups after the primary series (2.677 vs. 4.700 AU/mL, respectively,
P < 0.001), they were not different between the two groups after the booster vaccination
(7.246 vs. 7.979 AU/mL, respectively,
P = 0.108). In addition, the median IFN-γ concentration was higher in the BBB group
than in the CCB group (550.5 and 387.5 mIU/mL, respectively,
P = 0.014). There was also a difference in the cumulative incidence curves over time
(CCB group 50.0% vs. BBB group 41.8%;
P = 0.045), indicating that breakthrough infection occurred faster in the CCB group.
Conclusion
The cellular and humoral immune responses were low in the CCB group so that the breakthrough
infection occurred faster in the CCB group than in the BBB group.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail.
Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.
Background Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer–BioNtech, hearafter referred to as BNT). Methods COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY) control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130. Findings Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44–61) in the younger age group and 76 years (73–78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41–59) in the younger age group and 78 years (75–82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5–2·3) in the half VLA group to 32·3 (24·8–42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7–1·6) for ChAd to 3·6 (2·4–5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0–1·5) in the half VLA group to 11·5 (9·4–14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7–1·6) for half VLA to 4·7 (3·1–7·1) for m1273. The results were similar between those aged 30–69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30–69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273. Interpretation All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination. Funding UK Vaccine Taskforce and National Institute for Health Research.
[1
]Division of Infectious Diseases, Department of Internal Medicine, Chung-Ang University
Hospital, Seoul, Korea.
[2
]Department of Pediatrics, Chung-Ang University Hospital, Seoul, Korea.
[3
]Department of Laboratory Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong,
Korea.
[4
]Division of Infectious Diseases, Department of Internal Medicine, Chung-Ang University
Gwangmyeong Hospital, Gwangmyeong, Korea.
[5
]Department of Applied Statistics, Chung-Ang University, Seoul, Korea.
Author notes
Address for Correspondence: Jin-Won Chung, MD, PhD. Division of Infectious Diseases,
Department of Internal Medicine, Chung-Ang University Hospital, 102 Heukseok-ro, Dongjak-gu,
Seoul 06973, Korea.
drjwchung@
123456cau.ac.kr
*Seong-Ho Choi and Ji Young Park contributed equally as first authors.
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