[ad_1]
As many countries are hit hard by repeated waves of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with associated high rates of symptomatic coronavirus 2019 (COVID-19), the emergence more transmissible and possibly virulent variants challenge the success of current interventions.
Due to the high risk of mortality in the elderly and the frail, natural infection is not a viable option for the achievement of herd immunity. Instead, vaccines have been deployed around the world, in record time, in a courageous attempt to contain the pandemic.
A new pre-print, released on medRxiv* pre-print server, reports reduced vaccine efficacy following single dose use of vaccine in people on the immunosuppressive monoclonal antibody Infliximab.
Delayed dose protocols
With vaccine shortages, more and more countries are turning to delayed second dose protocols to optimize coverage. This compromise trades the efficacy of the vaccine for a larger vaccination network.
The study included more than 1,300 patients with inflammatory bowel disease, such as Crohn’s disease, who were being treated with Infliximab, when they received a dose of the Oxford / Astra-Zeneca ChAdOx1 nCoV vaccine. 19 or the BNT162b2 vaccine from Pfizer / BioNTech.
Previous research by the same scientists has shown that serological responses to SARS-CoV-2 infection are reduced or weakened in patients taking Infliximab, compared to another drug called vedolizumab.
Study details
The current study included 865 patients on Infliximab, a tumor necrosis factor (TNF) inhibitor, a potent pro-inflammatory molecule, and 428 patients on vedolizumab, an anti-integrin α4β7 monoclonal antibody with selective activity in the gut. , but no systemic immunosuppressive effect.
Deferred second-dose SARS-CoV-2 vaccination trades maximum efficacy for an immunity level below 54 in a larger portion of the population. We investigated whether patients with inflammatory bowel disease 55 treated with Infliximab attenuated serologic responses to a single dose of a SARS-CoV-2 vaccine 56.
We recently reported that seroprevalence, seroconversion in PCR-confirmed cases and magnitude 106 of anti-SARS-CoV-2 antibodies following SARS-CoV-2 infection are reduced in patients treated with Infliximab-107 compared to patients treated with vedolizumab.
What were the results?
At 3-10 weeks after vaccination, the study showed lower antibodies to the spike viral antigen, as well as lower seroconversion rates, in response to both vaccines, in the infliximab cohort, compared to the other. All of these patients had no history of infection with the virus.
Antibodies to lower peaks
The geometric mean anti-spike antibody concentrations in the former were 6 U / mL and 5 U / mL, with Pfizer and Oxford vaccines, respectively, in the infliximab cohort, compared to 29 U / mL and 14 U / mL, respectively, with vedolizumab.
When confounding variables were taken into account, antibody concentrations remained lower in the infliximab cohort, with a 0.3-fold change with the Pfizer vaccine compared to a 0.4-fold change with the Oxford vaccine.
People aged 60 or older, who were taking immunomodulatory drugs, had Crohn’s disease (but not ulcerative colitis or unclassified inflammatory bowel disease), or were current smokers, had high levels of antibodies anti-SARS-CoV-2 after a single dose of either vaccine. Conversely, non-white individuals had higher peak specific antibody titers.
Knockout of the TNF gene in mice leads to the rupture of B lymphocyte follicles within the germinal center, thereby affecting the production of specific antibodies. This could indicate that TNF inhibitors work in this way for the benefit of inflammatory bowel disease.
Seroconversion falls
Seroconversion has occurred in a greater proportion of patients after administration of one dose of either vaccine if the patient had a history of infection, as well as after administration of both doses of the vaccine. Pfizer.
Among patients with a history of infection with this virus, the geometric mean titer of anti-SARS-CoV-2 (S) antibodies was reduced in patients taking Infliximab compared to vedolizumab.
With one dose of Pfizer vaccine, the antibody concentration was 190 U / ml compared to 1,865 U / ml in the Infliximab vs. vedolizumab cohorts. With the Oxford vaccine, the corresponding concentrations were 185 and 752, respectively.
With both drugs and with both vaccines, the post-vaccination antibody titer of patients with previous infection was on average higher than that measured in naïve subjects. While 82% of the infliximab cohort seroconverted, 97% of those on vedolizumab did.
When two doses of Pfizer vaccine were given to naive patients, in either treatment group, antibody levels and seroconversion rates increased compared to a single dose in patients with no history. infection. The geometric mean titer for infliximab-treated patients with previous infection compared to vaccine-naive patients was 158 U / mL vs. 6 U / mL, while for vedolizumab it was 562 U / mL vs. 29 U / mL , respectively.
Seroconversion occurred in approximately 85% of the two cohorts (Infliximab and vedolizumab).
What are the implications?
The results of this study indicate that for patients on anti-TNF treatment, and in particular if an immunomodulator is also used, the serological responses to currently used vaccines are significantly altered after a single dose. This could lead to a higher risk of re-infection.
When two doses are used, conversely, the seroconversion rates are higher, indicating the need for all of these patients to receive both doses as planned, without delay in the second dose.
In addition, these patients should be considered still at risk after a single dose, and should therefore continue to limit their social interactions, and receive protection, if necessary.
The absence of seroconversion after two doses was noted in a small fraction of the group, and these patients may need revised vaccination schedules to ensure that they develop a protective immune response. These patients can only be identified by longitudinal measurement of the humoral response.
It will also help to estimate the durability of protective antibodies induced by vaccines.
Although these results are consistent with recent articles which report that the Pfizer vaccine and the Moderna vaccine are immunogenic in transplant patients and in cancer patients on anti-metabolite immunosuppressive drugs, chemotherapy or immunotherapeutic agents. Again, seroconversion was lower in patients receiving immunosuppressants than in healthy controls.
Two doses led to seroconversion even in tumor patients, but failure of seroconversion requires research on how to increase the immunogenicity of vaccines. Another problem associated with the failure of seroconversion in patients on immunosuppressants is the occurrence of chronic infection of the nasal tissues, leading to the emergence of new variants of SARS-CoV-2.
Future research should show whether this is a danger with infliximab treatment, which is associated with a failure of the antibody response.
The study also shows that smoking and aging are risk factors for an altered humoral response. Smoking has shown similar deleterious immune weakening effects in hepatitis B vaccine recipients. Again, influenza vaccines cause antibodies to decrease more rapidly.
Finally, non-whites appear to react more strongly to vaccines with a robust humoral response. Meanwhile, inhibition of TNF increases the risk of serious infection as well as opportunistic infections in these patients.
*Important Notice
medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behaviors, or be treated as established information.
Source link
