A prospective observational cohort study published in Viruses highlighted the pressing need for novel vaccination strategies against emerging variants of SARS-CoV-2, the virus responsible for the coronavirus disease 2019 (COVID-19), in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

The analysis of anti-S1 immunoglobulin G (IgG) and surrogate-neutralizing antibodies revealed decreased levels in patients with AAV following each administered vaccine dose (ie, first, second, and third), compared with healthy controls. Furthermore, neutralizing antibody activity was lower in patients with AAV than healthy controls after the second dose.

The study further underscored the deficiency of neutralizing immune responses against omicron subtypes BA.1 and BA.5 in patients with AAV.

“These data indicate that novel vaccination strategies, including adapted bivalent mRNA vaccines against epitopes of emerging variants, are needed to further protect high-risk individuals such as AAV patients. However, in the subgroup of patients treated with B-cell depletion therapy, additional booster vaccinations or adapted vaccine doses cannot be recommended based on the current data available,” the study’s authors said.

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In the AAV group, only 28% and 66% of patients had detectable anti-S1 IgG antibodies after the first and second vaccine doses, respectively, compared with 81% and 100% among healthy controls. Moreover, patients with AAV exhibited lower reactivity to various target epitopes following the standard 2-dose vaccination.

After the second vaccination, 61% of patients with AAV displayed triple positivity for anti-S1 IgG, surrogate-neutralizing antibodies, and anti-receptor binding domain (RBD) antibodies, whereas 23% exhibited no humoral immune response. This contrasted with 100% triple positivity seen in healthy controls.

Furthermore, patients with AAV receiving immunosuppressive maintenance therapy with steroids or mycophenolic acid/azathioprine exhibited higher levels of anti-S1 IgG, surrogate-neutralizing antibodies, and anti-RBD antibodies in contrast to those receiving the anti-CD20 monoclonal antibody rituximab.

After booster vaccination, both anti-S1 IgG and surrogate-neutralizing antibodies increased in patients with AAV and healthy controls. However, AAV patients maintained lower anti-S1 IgG and surrogate-neutralizing antibody levels compared with their healthy counterparts.

The study also affirmed the overall tolerability of different vaccine doses, with no observed AAV relapses during the follow-up period.

The research included 64 patients with AAV and 24 age- and vaccine-matched healthy controls, all enrolled prior to SARS-CoV-2 vaccination. Participants received either homologous or heterologous standard 2-dose vaccination employing mRNA or adenovirus-vectored vaccines.


Speer C, Töllner M, Benning L, et al. BA.1/BA.5 immunogenicity, reactogenicity, and disease activity after COVID-19 vaccination in patients with ANCA-associated vasculitis: a prospective observational cohort study. Viruses. Published online August 21, 2023. doi:10.3390/v15081778