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29th July 2021
Among immunocompromised individuals such as kidney transplant patients, a single COVID-19 vaccine dose has been found to elicit a sufficient response in only 17% of individuals. Furthermore, after a second dose, the response only increased to 54%. With evidence of a lower immune response to vaccination, the French National Authority for Health issued a recommendation in April 2021, that immunosuppressed, recent bone marrow transplant, those on dialysis, and patients with autoimmune diseases who did not respond after two doses of a COVID-19 vaccine, should be offered a third dose.
Given the evidence that even among kidney transplant patients who are fully vaccinated, severe COVID-19 can develop, a team from the Department of Nephrology and Transplantation, Strasbourg University Hospital, France, set out to assess the response to a third vaccination among kidney transplant patients who had an inadequate response to a second vaccination dose. The team examined the effect of the mRNA-1273 (Moderna) vaccine and included all kidney transplant patients who had no prior history of infection with COVID-19 and had anti-spike IgG antibody levels less than 50 arbitrary units, one month after administration of the second vaccination dose. They set a minimum antibody titre level of 50 units, so that any responses above this level could be considered as positive.
A total of 159 kidney transplant recipients with a median age of 57.6 years (61.6% male) and a median time from transplantation of 5.3 years were included in the analysis. After the second dose of vaccine, 59.7% (95) of patients had not generated an antibody response and the remaining patients showed a response below the positivity limit (6.8–49.9 units). The third vaccine dose was administered a median of 51 days after the second dose and the antibody response was then measured approximately 28 days after this third injection. However, at this time-point, only 49% of patients had antibody levels above 50 units. In addition, a response to the third vaccination was much more likely among those who had developed a response to the second dose (81.3% vs 27.4%, p = 0.01, second dose responders vs non-responders). The results also showed how kidney transplant patients prescribed a combination of tacrolimus, mycophenolate and steroids, were much less likely develop a response than those treated with other regimes (35% vs 63%, p = 0.006). No other factors such as sex, years since transplantation, or serum creatinine levels, had an effect on the development of an antibody response.
The authors reported on how despite three vaccination doses, 51% of kidney transplant patients failed to generate a positive antibody response and that this was more likely among those prescribed a triple therapy regime and concluded that kidney transplant patients should be offered a third vaccination dose.
Benotmane I et al. Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients with Minimal Serologic Response to 2 Doses. JAMA 2021
28th January 2021
The Moderna vaccine, mRNA-1273, has been shown to elicit high levels of neutralising antibody titres in clinical trials. However, with the identification of COVID-19 variants, a major concern is whether the range of vaccines available are capable of generating sufficient immunity. The UK COVID-19 variant, termed B.1.1.7, has 17 mutations, 8 of which are in the spike protein and two of which, 69-70 del and N501Y, have led to a particular concern that the variant is much more easily transmitted and potentially associated with a higher mortality. The other variant identified, B.1.351, has emerged from South Africa and as with the UK variant, evidence suggests that B.1.351 is more transmissible and produces a higher viral load among those who become infected. In fact, genomic analysis shows that mutations in the S protein are more extensive in B.1.351, with 3 of these present in the receptor binding domain, which is the target for neutralising antibodies which could affect vaccine efficacy. For this recent, but unpublished, study, researchers from Moderna, the vaccine manufacturer, sought to assess the neutralisation of sera from eight patients (aged 18 to 55) who had already received two doses of the company’s vaccine. In an effort to test the effectiveness of m-RNA-1273, the researchers created and tested pseudo viruses, that contained either a partial or a complete set of mutations present in the B.1.1.7 and B.1.351 lineages.
With respect to the B.1.1.7 lineage, both the partial and complete pseudo viruses, containing the recognised mutations, had minimal effect on the production of neutralising antibodies, i.e., the vaccine was just as effective against this variant as the original COVID-19 strain. In contrast, there was a significant decrease in neutralising titres measured against either the partial or complete mutations found within the B.1.351 variant. In fact, antibody titres were approximately 6-fold lower relative to other variants for the complete set of mutations. Nevertheless, the authors reported that the antibody titres generated against the complete B.1.351 pseudo virus, while lower than for B.1.1.7, were still generally high enough to provide protection if vaccinated with the mRNA-1273.
Wu K et al. mRNA-1273 induces neutralising antibodies against spike mutants from global SARS-CoV-2 variants. 2021 https://doi.org/10.1101/2021.01.25.427948https://doi.org/10.1101/2021.01.25.427948