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FDA green-lights third jab for immunocompromised people

The US Food and Drug Administration is poised to amend the emergency use authorisations for the Pfizer and the Moderna COVID-19 vaccines to allow people with compromised immune systems to get a third dose, according to NBC News.

The move comes after a panel of advisers to the Centers for Disease Control and Prevention (CDC) met in July and urged action on extra doses for immunocompromised adults.

Doctors say it is increasingly clear that many such patients are still vulnerable to COVID after vaccination because they may not mount an effective immune response to the shots.

An estimated 2.7% of adults in the US are immunocompromised, according to the CDC. It is unclear which groups would be covered under the FDA action. Immunocompromised patients include organ transplant recipients, people undergoing cancer treatment and people with HIV, among others.

Organ transplant recipients, for example, must take medication to suppress their immune systems so their bodies do not reject the new organs. One small study of these patients found the majority never developed antibodies to the coronavirus after vaccination. The others only developed low levels of protection.

In that study, (see below) from Johns Hopkins University, a third dose increased their antibody levels. A boost in immunity would probably be welcome to those who never had a good response from the  first two shots, as doctors have continued to advise such patients to continue with physical distancing and mask use, despite the vaccinations.

Study details
Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients
Brian J. Boyarsky, William A. Werbel, Robin K. Avery, Aaron A. R. Tobian, Allan B. Massie. Dorry L. Segev, Jacqueline M. Garonzik-Wang

Published in JAMA, 14 March 2021

Methods
Transplant recipients across the US were recruited though social media to participate in this prospective cohort, and those who underwent SARS-CoV-2 vaccination between December 16, 2020, and February 5, 2021, were included. The study was approved by the Johns Hopkins University institutional review board and participants provided informed consent electronically. Participants underwent either at-home blood sampling with the TAPII blood collection device (Seventh Sense Biosystems) or standard venipuncture.
The TAPII samples were tested using an enzyme immunoassay (EUROIMMUN) that tests for antibodies to the S1 domain of the SARS-CoV-2 spike protein. The venipuncture samples were tested using the anti–SARS-CoV-2 S enzyme immunoassay (Roche Elecsys) that tests for antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein. Both tests are semiquantitative, correspond to mRNA vaccine antigens, and are consistently correlated with neutralising immunity.

The sensitivity and specificity of the enzyme immunoassays are excellent for detection of the antispike humoral response to SARS-CoV-2 infection (sensitivity of 87.1% and specificity of 98.9% for EUROIMMUN3 and sensitivity of 84.0% and specificity of 100% for Roche Elecsys4) and are analogous to the antispike antibody assays used during immunogenicity assessments in mRNA vaccine clinical trials.

We assessed the proportion of patients who developed a positive antibody response with exact binomial 95% CIs. We evaluated the associations among demographic and clinical characteristics, vaccine type, and positive antibody response using modified Poisson regression with a robust variance estimator. A sensitivity analysis of vaccine type limited to those tested 14 to 21 days after vaccination was performed. All tests were 2-sided with α = .05. Analyses were performed using Stata version 16.1 (StataCorp).

Results
There were 436 transplant recipients included in the study. None had a prior polymerase chain reaction–confirmed diagnosis of COVID-19. The median age was 55.9 years (interquartile range [IQR], 41.3-67.4 years), 61% were women, and 89% were white transplant recipients; 52% received the BNT162b2 vaccine (Pfizer-BioNTech) and 48% received the mRNA-1273 vaccine (Moderna). The median time since transplant was 6.2 years (IQR, 2.7-12.7 years). The maintenance immunosuppression regimen included tacrolimus (83%), corticosteroids (54%), mycophenolate (66%), azathioprine (9%), sirolimus (4%), and everolimus (2%). At a median of 20 days (IQR, 17-24 days) after the first dose of vaccine, antibody (anti-S1 or anti–receptor-binding domain) was detectable in 76 of 436 participants (17%; 95% CI, 14%-21%).

Transplant recipients receiving anti–metabolite maintenance immunosuppression therapy were less likely to develop an antibody response than those not receiving such immunosuppression therapy (37% vs 63%, respectively; adjusted incidence rate ratio [IRR], 0.22 [95% CI, 0.15-0.34]; P < .001) (Table). Older transplant recipients were less likely to develop an antibody response (adjusted IRR, 0.83 [95% CI, 0.73-0.93] per 10 years; P = .002). Those who received mRNA-1273 were more likely to develop an antibody response than those receiving BNT162b2 (69% vs 31%, respectively; adjusted IRR, 2.15 [95% CI, 1.29-3.57]; P = .003). This association was similar in a sensitivity analysis limited to those tested 14 to 21 days after vaccination (n = 245; adjusted IRR, 2.29 [95% CI, 1.32-3.94]; P = .003).

Discussion
In this study of immunogenicity of the first dose of the mRNA SARS-CoV-2 vaccine among solid organ transplant recipients, the majority of participants did not mount appreciable antispike antibody responses. However, younger participants, those not receiving anti–metabolite maintenance immunosuppression, and those who received the mRNA-1273 vaccine were more likely to develop antibody responses.

These results contrast with the robust early immunogenicity observed in mRNA vaccine trials, including 100% antispike seroconversion by day 15 following vaccination with mRNA-12735 and by day 21 following vaccination with BNT162b2.6. Limitations include a convenience sample that may lack generalizability, lack of serial measurements after vaccination, and lack of a concurrent control group without immunosuppression. In addition, these data represent the humoral response to the first dose of a 2-dose series.

These findings of poor antispike antibody responses in organ transplant recipients after the first dose of mRNA vaccines suggest that such patients may remain at higher early risk for COVID-19 despite vaccination. Deeper immunophenotyping of transplant recipients after vaccination, including characterisation of memory B-cell and T-cell responses, will be important in determining vaccination strategies as well as immunologic responses after the second dose.

 

NBC article – FDA poised to OK 3rd vaccine dose for immunocompromised people (Open access)

 

JAMA article – Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients (Open access)

 

See more from MedicalBrief archives:

 

WHO’s vaccine head on why the rush for COVID booster jabs is premature

 

COVID-19 vaccines highly effective in most people in clinical risk groups — Massive UK study

 

Moderna modifying COVID-19 vaccine to protect against emerging strains

 

COVID antibody levels boosted sixfold with mixed AstraZeneca-Pfizer shot

 

 

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