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1.
Nature ; 607(7917): 128-134, 2022 07.
Article in English | MEDLINE | ID: covidwho-1805634

ABSTRACT

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals1-3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection4. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses5,6. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Memory B Cells , SARS-CoV-2 , mRNA Vaccines , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Humans , Memory B Cells/immunology , RNA, Messenger/genetics , SARS-CoV-2/genetics , SARS-CoV-2/immunology , mRNA Vaccines/administration & dosage , mRNA Vaccines/immunology
2.
Cell Rep ; 38(9): 110429, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1734242

ABSTRACT

Continuous emergence of SARS-CoV-2 variants of concern (VOCs) is fueling the COVID-19 pandemic. Omicron (B.1.1.529) rapidly spread worldwide. The large number of mutations in its Spike raise concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses elicits antibodies that efficiently recognize Spikes from different VOCs. Here, we evaluate the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously infected individuals who received their BNT162b2 mRNA vaccine 16 weeks apart. Omicron Spike is recognized less efficiently than D614G, Alpha, Beta, Gamma, and Delta Spikes. We compare with plasma activity from participants receiving a short (4 weeks) interval regimen. Plasma from individuals of the long-interval cohort recognize and neutralize better the Omicron Spike compared with those who received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.


Subject(s)
Antibodies, Neutralizing/blood , BNT162 Vaccine/administration & dosage , Immunization Schedule , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Antibodies, Neutralizing/analysis , Antibodies, Neutralizing/immunology , Antibodies, Viral/analysis , Antibodies, Viral/blood , Antibodies, Viral/immunology , BNT162 Vaccine/immunology , Cohort Studies , Female , HEK293 Cells , Humans , Immunization, Secondary/methods , Male , Middle Aged , Quebec , SARS-CoV-2/pathogenicity , Time Factors , Vaccination/methods , Vaccine Potency , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Young Adult , mRNA Vaccines/administration & dosage , mRNA Vaccines/immunology
4.
Cell Rep ; 38(5): 110336, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1661802

ABSTRACT

Understanding vaccine-mediated protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to overcoming the global coronavirus disease 2019 (COVID-19) pandemic. We investigate mRNA-vaccine-induced antibody responses against the reference strain, seven variants, and seasonal coronaviruses in 168 healthy individuals at three time points: before vaccination, after the first dose, and after the second dose. Following complete vaccination, both naive and previously infected individuals developed comparably robust SARS-CoV-2 spike antibodies and variable levels of cross-reactive antibodies to seasonal coronaviruses. However, the strength and frequency of SARS-CoV-2 neutralizing antibodies in naive individuals were lower than in previously infected individuals. After the first vaccine dose, one-third of previously infected individuals lacked neutralizing antibodies; this was improved to one-fifth after the second dose. In all individuals, neutralizing antibody responses against the Alpha and Delta variants were weaker than against the reference strain. Our findings support future tailored vaccination strategies against emerging SARS-CoV-2 variants as mRNA-vaccine-induced neutralizing antibodies are highly variable among individuals.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Cross Reactions , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Coronavirus/immunology , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , mRNA Vaccines/administration & dosage , mRNA Vaccines/immunology
5.
BJOG ; 129(1): 21-28, 2022 01.
Article in English | MEDLINE | ID: covidwho-1612816

ABSTRACT

The novel coronavirus, SARS-CoV-2, or COVID-19, has affected the world on a pandemic scale resulting in catastrophic outcomes and deaths. Currently, there is limited safety data specific to mRNA vaccine use in pregnant or lactating individuals and the potential risks to a pregnant individual and the fetus are unknown. We report an updated literature review of current information and evidence available to aid in the decision whether to vaccinate against COVID-19 currently being made by pregnant individuals and their healthcare providers so that they are able to make a well-informed recommendation and decision.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Pregnancy Complications, Infectious/prevention & control , Prenatal Care , mRNA Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Female , Humans , Pregnancy , mRNA Vaccines/adverse effects
6.
Lancet ; 399(10319): 36-49, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1557000

ABSTRACT

BACKGROUND: Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer-BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). METHODS: Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8-12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. FINDINGS: Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation. INTERPRETATION: Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification. FUNDING: UK Vaccine Task Force, Coalition for Epidemic Preparedness Innovations (CEPI), and National Institute for Health Research. NVX vaccine was supplied for use in the trial by Novavax.


Subject(s)
Adjuvants, Vaccine/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Immunization, Secondary/adverse effects , Immunization, Secondary/methods , Immunogenicity, Vaccine , mRNA Vaccines/administration & dosage , 2019-nCoV Vaccine mRNA-1273/administration & dosage , 2019-nCoV Vaccine mRNA-1273/immunology , Aged , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , ChAdOx1 nCoV-19/administration & dosage , ChAdOx1 nCoV-19/immunology , Female , Humans , Male , Middle Aged , Single-Blind Method , United Kingdom , Vaccination/adverse effects , Vaccination/methods , mRNA Vaccines/immunology
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