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We investigated 68 respiratory specimens from 35 coronavirus disease patients in Hong Kong, of whom 32 had mild disease. We found that severe acute respiratory syndrome coronavirus 2 and subgenomic RNA were rarely detectable beyond 8 days after onset of illness. However, virus RNA was detectable for many weeks by reverse transcription PCR.
Omicron, a novel SARS-CoV-2 variant has emerged and is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in serum of convalescent or vaccinated individuals to understand potential loss of protection from infection or re-infection. Two doses of BNT162b2 or CoronaVac vaccines provided little 50% plaque reduction neutralization test (PRNT50) antibody immunity against the Omicron variant, even at one-month post vaccination. Booster doses with BNT162b2 in those with two doses of either BNT162b2 or CoronaVac provided acceptable neutralizing immunity against Omicron variant at 1-month post-booster dose. However, three doses of BNT162b2 elicited higher levels of PRNT50 antibody to Omicron variant suggesting longer duration of protection. Convalescent from SARS-CoV-2 infection did not have protective PRNT50 antibody levels to Omicron, but a single dose of BNT162b2 vaccine provided protective immunity. Field vaccine-efficacy studies against Omicron variant against different vaccines are urgently needed.
In 68 respiratory specimens from a cohort of 35 COVID-19 patients, 32 of them with mild disease, we found SARS coronavirus-2 virus culture and sub-genomic RNA was rarely detectable beyond 8 days after onset of illness although virus RNA by RT-PCR remained detectable for many weeks.
Limited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants. We conducted an open label trial and administered a third vaccine dose of an mRNA vaccine (BNT162b2, BioNTech/Fosun Pharma) in adults aged ≥30 years who had previously received two doses of an inactivated COVID-19 vaccine. We collected blood samples prior to administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT), and to the Omicron variant using PRNT. A third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.1 (p<0.01), and mean sVNT levels increased from an inhibition of 17% to 96% (p<0.01). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by at least 27 fold from Day 0 to Day 28 against the ancestral virus (p<0.01) and rose by at least 14 fold against the Omicron variant (p<0.01). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants. In conclusion, a third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and against the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier.
Background
Limited data exist on antibody responses to mixed vaccination strategies that involve inactivated coronavirus disease 2019 (COVID-19) vaccines, particularly in the context of emerging variants.
Methods
We conducted an open-label trial of a third vaccine dose of a messenger RNA (mRNA) vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received 2 doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later and tested for antibodies to the ancestral virus using a binding assay (enzyme-linked immunosorbent assay [ELISA]), a surrogate virus neutralization test (sVNT), and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT.
Results
In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density of 0.3 to 2.2 (P < .001), and mean sVNT levels increased from an inhibition of 17% to 96% (P < .001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose substantially, by 45-fold from day 0 to day 28 against the ancestral virus (P < .001) and by 11-fold against the Omicron variant (P < .001). In daily monitoring, post-vaccination reactions subsided within 7 days for more than 99% of participants.
Conclusions
A third dose of COVID-19 vaccine with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with a well-tolerated safety profile in adults who had received 2 doses of inactivated vaccine 6 months earlier.
Clinical Trials Registration
NCT05057182.
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