Dialysis patients that received the Pfizer vaccine had six-times higher levels of neutralizing antibodies against the Delta variant compared to those vaccinated with the Oxford-AstraZeneca vaccine

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Patients receiving in-hospital dialysis treatment for kidney disease produce a larger neutralizing antibody response when given the Pfizer-BioNTech COVID-19 vaccine, compared to the Oxford-AstraZeneca vaccine, according to laboratory findings published today (Thursday) as a Correspondence in The Lancet.

It is reported that immunocompromised patients will be prioritized to receive a third dose of vaccine in the autumn, so researchers have submitted their findings to the Joint Committee on Vaccination and Immunisation (JCVI) as evidence of how best to protect this vulnerable group.

Levels of antibodies alone do not predict vaccine effectiveness and researchers are confident that for most, a complete course of either vaccine will still protect against severe disease or death.

As part of the study, led by the Francis Crick Institute and Imperial College London, the research team examined blood samples from 178 patients receiving haemodialysis treatment.

Funded by Kidney Research UK, the National Kidney Federation, Kidney Wales, the PKD Charity and several Kidney Patient Associations, the project includes patients from across the UK and will, in time, report on over 1,000 haemodialysis patients.

The researchers used robust high throughput viral neutralization assays (laboratory tests), developed at the Crick, to test the ability of antibodies to block entry of the virus into cells, so called ‘neutralizing antibodies’, against different variants of SARS-CoV-2, including Delta.

In patients who had not been previously infected with SARS-CoV-2, those who had received the Pfizer-BioNTech mRNA vaccine had six-times higher levels of neutralizing antibodies against the Delta variant, compared to those vaccinated with the Oxford-AstraZeneca vaccine. The levels induced by the mRNA vaccine were comparable to those seen in healthy controls after both vaccine doses.

In patients who had evidence of infection prior to vaccination, both vaccines induced detectable levels of neutralizing antibodies.

These findings suggest that patients who have not been infected with SARS-CoV-2 previously and received the Oxford-AstraZeneca vaccine, would likely benefit from an early third dose of an alternative mRNA vaccine.

Edward Carr, postdoctoral clinical fellow in the Crick’s Cell Biology of Infection Laboratory, says that “unfortunately, the risk from COVID-19 has been much greater for dialysis patients as we’ve seen high rates of admissions and deaths in this group.

The level of neutralizing antibody to Delta made by haemodialysis patients, who have not had a prior COVID infection and received the Oxford-AstraZeneca vaccine, might not be enough to prevent infection with Delta.”

“Importantly, we’ve found that this group (without prior infection) respond well to mRNA vaccines and we can use this information to inform future vaccination strategies.”

Dr. Aisling McMahon, Executive director of Research, Innovation and Policy at Kidney Research UK, which co-funded the study, said that “this is extremely timely research. We already know that many kidney patients respond less well to vaccines than the general population.

The good news is that both these vaccine technologies are protecting people from serious illness. However, many dialysis patients still need to travel to hospital several times a week for life-saving treatment and so remain more at risk of catching Covid-19.”

“These findings clearly indicate that dialysis patients (who have not previously had Covid-19) are unlikely to be adequately protected from the delta variant if they received the AZ vaccine. We believe that this study provides strong evidence to support a third dose of an mRNA vaccine as standard treatment as soon as possible for all immunocompromised patients who potentially remain at risk.”

Rupert Beale, head of the Crick’s Cell Biology of Infection Laboratory, said that “the vaccination program in the UK has been a huge success, but the pandemic isn’t over. As most people enjoy increased freedom, many immunocompromised patients remain vulnerable. Our data suggest that delivering a third dose of vaccine will be necessary to protect some patient groups.”

Dr. Michelle Willicombe, Clinical Senior Lecturer at Imperial College London and Honorary Consultant Nephrologist at Imperial College Healthcare NHS Trust, and Dr. Stephen McAdoo, Honorary Clinical Senior Lecturer at Imperial College London and Consultant Nephrologist at Imperial College Healthcare NHS Trust, co-lead the UK Kidney Association vaccine efficacy group which awarded funding for the study.

Dr. Willicombe said that “the collaborative involvement from kidney health professionals and patients in this study demonstrates the need and common goal of trying to optimize protection for people with kidney disease, who have been disproportionately affected by COVID-19.”


Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with higher morbidity and mortality in patients on maintenance hemodialysis (HD) (1,2).

Prioritizing patients on dialysis for vaccination has been at the forefront of SARS-CoV-2 vaccination programs internationally (3). Patients with CKD, but especially those with kidney failure, treated with maintenance HD tend to have a reduced immune response to infection or vaccination, as demonstrated with the hepatitis B virus vaccine. Consequently, there is often a need for higher vaccine dosage or scheduling changes in these patients (4 ⇓–6).

Several vaccines have been approved for SARS-CoV-2 infection. Live attenuated vaccines generally should be avoided in patients on maintenance HD due to their dysregulated immune system. Both the mRNA vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) and the replication-defective viral-vectored vaccines, such as ChAdOx1 nCoV-19 (Oxford-AstraZeneca), are considered safe for use in patients treated with maintenance HD (7,8).

This study is aimed at establishing one aspect of the immune response, the humoral response to the BNT162b2 (Pfizer-BioNTech) vaccine in patients with kidney failure on maintenance HD. We determined the level of antibodies directed against the spike antigen following vaccination of patients on maintenance HD and compared it with controls with no kidney failure, searching for factors that may be associated with the humoral response.

Discussion

In this study, we describe, for the first time to the best of our knowledge, the IgG antibody response to the spike protein following vaccination with the BNT162b2 (Pfizer-BioNTech) vaccine in patients on maintenance HD compared with a cohort vaccinated health care workers. The pivotal trial that demonstrated 95% protection against COVID-19 infection following a two-dose regimen of the BNT162b2 vaccine did not include patients on maintenance HD (12).

It is well known that patients on dialysis may have a reduced response to vaccination. We, therefore, aimed to assess this assumption regarding the BNT162b2 (Pfizer-BioNTech) vaccine.

Our major finding is that the majority of patients on maintenance HD developed a substantial humoral response following the two vaccine doses; however, it was significantly lower than controls.

The cutoff for a positive response in our assay was 50 AU/ml, and >90% of our cohort was well above this threshold. Interestingly, one of the two subjects who did not develop a response reported long-term prednisone use. Other patients were treated with prednisone and responded; therefore, this alone did not explain the lack of response in the one patient.

Preliminary reports have shown a lack of humoral response following vaccination with the mRNA-1273 vaccine (Moderna) and the BNT162b2 vaccine (Pfizer-BioNTech) in patients with transplants treated with long-term immunosuppression (13). This may warrant further studies on the timing and efficacy of vaccination in patients treated with immunosuppressants.

When comparing the groups and data within groups, age is a substantial factor in determining the level of response.

There was little difference between the antibody response in vaccinees older than 70 years of age in the dialysis group compared with the control group, implying that age is an important factor in humoral response, regardless of chronic medical conditions.

We did find a correlation between the level of antibodies and lymphocyte count. This is not surprising given the lymphocyte role in the immune system in general and the production of antibodies in particular (14). The role of the cellular arm in the immune response following vaccination with the BNT162b2 vaccine remains to be elucidated.

We found no association between the level of IgG response and body mass index, dialysis dose, dialysis vintage, transplantation candidacy status, or albumin levels.

Although our findings are preliminary and warrant further clarifications and verifications, we believe these findings should prompt consideration following further information for changing the dose/schedule of vaccinations in patients on maintenance HD as has been done with different vaccines in the past: for example, with the hepatitis B vaccine Engerix-B, which is given in double doses as a four-series vaccine instead of a three-series vaccine in healthy individuals (15,16).

Further assessments of other parts of the immune response are needed, mainly assessing the cellular response. However, it is difficult to assume that the cellular immune response will fare better (17,18).

Although the level of the humoral response in most patients on maintenance HD in our study is considered positive, the weaker seroresponse (relative to controls and the populations in which the vaccine trials were conducted) may have consequences, including lower vaccine efficacy to the parent strain or to variants that are evolving and/or a shorter period of immunoprotection after vaccination. Studies to assess vaccine efficacy, antibody waning, and efficacy against variants in this population are needed (19).

Our study has several limitations. Size of the study is an inherent limitation in this study. Given the need to perform the assay in close proximity to the vaccine schedule, we were not able to recruit more centers in this study.

In many countries, incidence and/or severity of COVID-19 have varied by ethnicity, which we could not investigate due to the homogenous nature of our maintenance HD population.

Furthermore, there is a considerable age difference between the dialysis group and the control group that stems from the nature of both populations (health care workers versus patients on maintenance HD). We tried to overcome this limitation by adjusting the statistical analysis for age and by dividing into similar age groups in both cohorts.

We did not perform baseline antibody titers, and thus, we cannot exclude the possibility that the seroresponse results may reflect infection versus vaccination in some patients. However, we tested (using PCR) patients presenting with symptoms, contacts of SARS-CoV-2–positive patients, and the entire shift in the case of a positive case from that shift. The last PCR test prior to the vaccine was 59±29 days on average.

Although this is one of our limitations because we cannot rule out asymptomatic infection, we have not detected any asymptomatic infection in our unit during the previous 12 months, and patients on dialysis have been reported to have a low rate of asymptomatic infection (<10%) (20).

The clinical implications of the serology test and the presence of antibodies and their levels remain to be fully clarified. There are several reports regarding the correlation of antibodies to SARS-CoV-2. Lumley et al. (21) followed 12,541 health care workers, of whom 1265 were seropositive for antispike IgG following infection with SARS-CoV-2 and demonstrated a substantially reduced risk for reinfection 6 months following infection. Bartsch et al. (22) describe a relationship between antibody titers and functional antibody activity to SARS-CoV-2 over time. Regarding protection following vaccine, there is a recent study in press that presents that neutralization level is highly predictive of immune protection.

In conclusion, patients on maintenance HD develop a substantial humoral immune response following the BNT162b2 vaccine. This finding is reassuring and should encourage patients on maintenance HD and their caregivers to receive the vaccine, especially considering the safety profile emerging from real-world data regarding the vaccine.

reference link : https://cjasn.asnjournals.org/content/16/7/1037


More information: Edward J Carr et al, Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients, The Lancet (2021). DOI: 10.1016/S0140-6736(21)01854-7

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