Immunogenicity and benefits of third shot

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New data presented at ACR 2021 shows a covid vax booster improved immunogenicity in rituximab patients.

Recent research – including late breaking abstracts at ACR21 – sheds further light on covid vaccine immunogenicity in rheumatology patients and the effectiveness of a third dose in rituximab patients.

While covid vaccines have robust immunogenicity in the general population, data in people receiving immunosuppressants is still lacking, said Dr Satveer Mahil, a consultant dermatologist and senior lecturer at St John’s Institute of Dermatology in London.

“These patients were excluded from trials of covid vaccines and had been shielding for large parts of the pandemic due to ongoing concerns over their risks of adverse covid outcomes,” she said.

“Emerging research on the covid vaccines in the context of immunosuppression has focused on seroconversion, which is not representative of the complex immune response to vaccines and may not correlate with clinical effectiveness.”

Dr Mahil and colleagues studied the impact of monotherapy with methotrexate or biologics targeting TNF, IL-17 and IL-23, on humoral and cellular immunogenicity to a single and double dose of the Pfizer covid vaccine.

They found that methotrexate, but not biologics, impaired functional humoral immunity to a single dose of the vaccine, while cellular responses were similar, with a proportion of the control and immunosuppressed cohorts having undetectable T-cell responses.

However, serological and functional humoral responses at 14 days following the second dose were not significantly impaired by methotrexate or biologic monotherapy. Participants undergoing immunosuppressing therapy had similar anti-spike IgG titres and functional humoral response to controls.

T-cell response rates after the first dose of the vaccine were similar in patients receiving immunosuppressing therapy and in controls, with a proportion of people in each study group failing to mount a response.

However, while 100% of healthy participants mounted a T-cell response following the second dose, only 71% of those receiving immunosuppressants did.

“The data certainly support the prioritisation of patients receiving therapeutic immunosuppression to receive a further dose of the vaccine,” said Dr Mahil.

According to Dr Michael Bonelli from the Medical University of Vienna, who also presented at ACR 2021, patients taking rituximab might also benefit from a third (booster) shot.

He and his team investigated rituximab’s effect on vaccination response in a cohort of 74 patients receiving the medication.

They found that only about 40% of patients taking rituximab mounted a humoral immune response after two doses of an mRNA covid vaccine.

They also observed that shorter times between the last rituximab treatment and vaccination was correlated with a lower response.  “We should be careful when we prescribe rituximab,” said Dr Bonelli. “In patients who are clinically stable, we might consider postponing rituximab.”

About 30% of patients developed neither humoral nor cellular immune responses.

Consequently, they ran a blinded randomised clinical trial to compare the efficacy and safety of an additional booster vaccination in non-seroconverted patients.

The researchers randomised 60 patients under rituximab treatment to receive a third dose of either the same mRNA vaccine they had previously received or the Oxford-AstraZeneca vector vaccine.

Four weeks after receiving the booster shot, about 22% of patients who received the Oxford-AstraZeneca vaccine seroconverted, compared with 32% of patients who received the mRNA vaccine.

All patients who received the Oxford-AstraZeneca vaccine and 81% of those who received the mRNA vaccine mounted a T-cell response. Almost all patients developed either humoral or cellular immune response or both, reducing the portion of patients who did not develop any response from 30% following primary vaccination to 6% following the third dose.

The booster also proved to be safe, with no serious adverse events reported.

“Antibody production is possible in non-seroconverted immunosuppressed patients who failed to respond to primary vaccination,” Dr Bonelli said. “We, therefore, recommend an additional boost of vaccination for rituximab patients, irrespective of a heterologous or homologous vaccination regimen.”

In other recent research on immunogenicity and anti-CD20 therapy, a Swiss study published last week in Clinical Infectious Diseases assessed humoral and T-cell responses after two doses of an mRNA vaccine in 11 rheumatic disease patients taking rituximab and 26 multiple sclerosis patients taking ocrelizumab. A group of 22 age-matched immunocompetent people served as controls.

The prospective observational cohort study found that despite impaired humoral responses, most patients were able to mount robust T-cell responses to the vaccine.

Around 73% of the rheumatic disease patients had detectable antibodies, and these were present at levels lower than the controls. The rheumatic disease patients with undetectable antibodies had received concomitant treatment with methotrexate or corticosteroids.

On the other hand, around 82% of rheumatic disease patients produced strong spike-specific T-cell responses – a higher response rate than the controls (67%) though lower than MS patients on ocrelizumab (96%). Furthermore, the T cells were polyfunctional, producing at least two or three cytokines.

The authors noted that T-cell immunity against SARS-CoV-2 is believed – though not proven – to help protect against severe disease. They suggested this could play an important role in reducing the complications of severe covid, but said the study wasn’t designed to correlate T-cell findings with clinical protection.

However, in the context of disproportionate representation of rituximab-treated patients amongst severe disease and death in the US, even after vaccination, others have questioned what protection a standard vaccination schedule offers patients concomitantly on rituximab.

Limitations included the small number of patients in each group and short follow-up after vaccination.

  • L18 Humoral and Cellular Immune Responses to a Second Dose of COVID-19 Vaccine BNT162b2 in People Receiving Methotrexate or Targeted Immunosuppression: A Cohort Study
  • L17 Additional Heterologous versus Homologous Booster Vaccination in Immunosuppressed Patients Without SARS-CoV-2 Antibody Seroconversion After Primary mRNA Vaccination: A Randomized Controlled Trial

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