Antibody response to COVID-19 booster vaccine in rituximab-treated patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

To the editor:

The success of the infectious coronavirus disease 2019 (COVID-19) vaccine has been accompanied by challenges, which include suboptimal response in patients on immunosuppression. Although booster doses of the vaccine have led to an increment in the number of patients (solid organ transplant recipients and patients with rheumatic disease) achieving an antibody response, a considerable proportion continue to demonstrate none. , Although it is known that the administration of rituximab is associated with a lower response to the initial vaccine series, there is a paucity of data regarding its effect with respect to booster doses. We looked to ascertain the antibody response after booster vaccine doses in patients with anti–neutrophil cytoplasmic antibody–associated vasculitis on maintenance rituximab, who had no response to the initial vaccine series.

Anti–neutrophil cytoplasmic antibody–associated vasculitis patients attending the vasculitis clinic at Johns Hopkins on rituximab therapy were screened for a completion of a vaccine series and associated negative antibody response between January 2021 and September 2021. IgG antibodies to the spike protein S1 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured using enzyme-linked immunosorbent assay at least 1 month after completion of a vaccination series and booster doses. Clinical demographics and immunologic data were retrieved after review of the electronic health record. Fifteen patients with no demonstrable antibody response received a booster dose. B-cell depletion was defined as the absolute CD19 count of 0/mm3. This study was approved by the Johns Hopkins Institutional Review Board.

Of the 15 patients, 7 had a discernable antibody response to a booster dose (Table 1 ). The median age (interquartile range) was 69 (62–73) years, with 7 patients being female and 8 with granulomatosis with an angiitis phenotype (the rest of the patients had microscopic polyangiitis). Seven patients received the Pfizer–BioNTech vaccine, with 6 and 2 patients receiving the Moderna and Johnson & Johnson vaccine, respectively (patients who initially received Pfizer or Moderna completed the same booster types). All patients had CD19 depleted at the time of completion of first vaccine series, with 5 of 7 booster-dose responders having B-cell reconstitution at the time of the administration of third dose of the vaccine. Of note, the 2 patients who demonstrated an antibody response despite complete B-cell depletion initially received the Johnson & Johnson vaccine and received a booster Pfizer or Moderna doses.

Table 1

Patient characteristics, IS regimen, immunologic data, and details of vaccine administration

ID	Age, yr	Sex	Ethnicity	ANCA type	Disease duration elapsed since booster, yr	Vaccine type	SP Ab after second dose	CD19 levels at the time of second dose, %	Booster vaccine type	Duration elapsed between first vaccine series and third vaccine dose, mo	SP Ab post third dose	CD19 levels at the time of third dose	Relation of last RTX dose to first dose, mo	Relation of last RTX dose to third dose, mo	IS regimen
1	66	M	W	PR3	4	J&J	N	<1	Pfizer	3	P	U	–4	–8	RTX
2	80	F	W	MPO	6	J&J	N	<1	Moderna	4	P	U	–4	–9	RTX
3	69	F	W	MPO	8	Pfizer	N	<1	J&J	3	N	U	–2	–6	RTX
4	66	F	W	PR3	3	Moderna	N	<1	Moderna	5	P	R	–3	–10	RTX
5	69	F	W	PR3	3	Pfizer	N	<1	Pfizer	6	N	U	–1	–8	RTX
6	69	F	W	PR3	6	Pfizer	N	<1	Pfizer	6	N	R	–5	–11	RTX + S
7	73	M	W	MPO	8	Moderna	N	<1	Moderna	7	P	R	–4	–11	RTX
8	55	M	W	MPO	4	Moderna	N	<1	Moderna	6	P	R	–3	–10	RTX
9	50	M	W	PR3	21	Moderna	N	<1	Moderna	6	N	U	–2	–9	RTX + S + SQIG
10	61	M	W	PR3	1	Pfizer	N	<1	Pfizer	4	N	U	–7	–11	RTX
11	65	M	W	MPO	7	Pfizer	N	<1	Pfizer	6	N	U	–6	–12	RTX
12	62	M	W	PR3	7	Pfizer	N	<1	Pfizer	4	P	R	–5	–10	RTX
13	74	F	W	MPO	4	Moderna	N	<1	Moderna	8	P	R	–1	–9	RTX
14	79	M	W	PR3	7	Pfizer	N	<1	Pfizer	1	N	U	–5	–6	RTX
15	73	F	A	MPO	5	Moderna	N	<1	Moderna	5	N	U	–1	–7	RTX

A, African American; Ab, antibody; ANCA, anti–neutrophil cytoplasmic antibody; F, female; ID, identifier; IS, immunosuppression; J&J, Johnson & Johnson; M, male; MPO, myeloperoxidase; N, negative; P, positive; PR3, proteinase 3; R, reconstitution; RTX, rituximab; S, corticosteroids; SP, spike protein; SQIG, subcutaneous immunoglobulin; U, undetectable; W, White.

To our knowledge, this is the largest study to elucidate the antibody response to a COVID-19 vaccine booster dose in patients on rituximab therapy. These data consolidate the recommendation that it is imperative that patients receiving rituximab therapy should receive a booster dose to aid in the generation of an immune response. As with previous data on booster doses in patients on immunosuppressive therapy, a considerable number of patients did not have a discernible antibody response. , B-cell reconstitution correlated with an antibody response to boosters in most patients; however, 2 patients with complete B-cell depletion warrant further discussion. These 2 patients received Johnson & Johnson as the initial vaccine with a subsequent Moderna or Pfizer booster series. This is keeping with encouraging reports of improving immunogenicity with combining different types of vaccines, especially in patients who are with immunocompromise. This could be a viable strategy in generating an immune response in patients with B-cell depletion as consequence of rituximab, thus balancing the need for primary disease control with continued therapy and achieving an essential goal of vaccine immune response in a vulnerable population.

Disclosure

DG is a consultant to ChemoCentryx and Aurinia Inc. All the other authors declared no competing interests.