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Cell Reports Medicine ; : 100739, 2022.
Article in English | ScienceDirect | ID: covidwho-2004612


Age is the strongest determinant of COVID-19 mortality and over 2 billion people have received primary series vaccination with BNT162b2 (mRNA) or ChAdOx1 (adenoviral vector). However, the profile of sustained vaccine immunogenicity in older people is unknown. Here we determine spike-specific humoral and cellular immunity to 8 months following BNT162b2 or ChAdOx1 in 245 people aged 80-98 years. Vaccines are strongly immunogenic with antibodies retained in every donor whilst titers fall to 23-26% from peak. Peak immunity develops rapidly with standard interval BNT162b2 although antibody titers are enhanced 3.7-fold with extended interval. Neutralisation of ancestral variant is superior following BNT162b2 whilst neutralisation of Omicron is broadly negative. Conversely, cellular responses are stronger following ChAdOx1 and retained to 33-60% of peak with all vaccines. BNT162b2 and ChAdOx1 elicit strong but differential sustained immunogenicity in older people. These data provide a baseline to assess optimal booster regimen in this vulnerable age group.

EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318752


Background: B cell chronic lymphocytic leukaemia (CLL) is associated with immune suppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination.Methods: We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 13 patients underwent a standard interval (3-week) vaccine regimen whilst 286 underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. 267 samples were taken at 5 weeks after the first vaccine for patients on the extended interval regimen and 13 and 42 samples were taken at 2-4 weeks after the second vaccine in patients on the standard or extended vaccine regimens respectively.Findings: Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine, compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine.Interpretation: Antibody responses after both the first and second Covid-19 vaccine are lower in patients with CLL compared to age-matched donors. This is particularly marked in patients who are taking BTK inhibitors or have serum IgA deficiency. Further approaches such as repeat vaccination or administration of prophylactic antibody may be worthy of investigation for some patients. Funding Information: This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.Declaration of Interests: None to declare. Ethics Approval Statement: The work was performed under the CIA UPH IRAS approval (REC 20W\0240) and conducted according to the Declaration of Helsinki and good clinical practice. Ethical approval was obtained from North West Preston Research Ethics Committee with favourable outcome. Informed consent was obtained in person or by remote consultation.

EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295697


Background: Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL) and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses.<br><br>Method: We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with 2 different vaccine platforms.<br><br>Results: Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n=204) or adenovirus-based (n=296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months-post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination.<br><br>Interpretation: These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoral protection against the globally-dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.<br><br>Funding Information: This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.<br><br>Declaration of Interests: The authors declare no conflicts of interest.<br><br>Ethics Approval Statement: Informed consent was obtained by remote consultation and work performed under the CIA UPH IRAS approval (REC 20W\0240) from North-West and Preston ethics committee and conducted according to the Declaration of Helsinki.<br>