Victoria G. Hall

Complement inhibitor therapy carries a risk of serious infections, including meningococcal disease. Here we provide evidence‐based recommendations and expert consensus for immunisation and prophylactic treatment of patients receiving, or planning to receive, complement inhibitors for neurological conditions in the Australian setting. The primary aim of these consensus recommendations is to minimise the risk of vaccine‐preventable infections and to outline alternative infection‐prevention strategies where vaccination is problematic. We address disease‐specific risks and propose timing considerations, including a pragmatic approach to clinical implementation.

Background: Solid organ transplant (SOT) recipients are at increased risk for severe COVID‐19 and often exhibit reduced vaccine efficacy due to chronic immunosuppression. As new SARS‐CoV‐2 variants emerge, understanding immune responses following natural infection remains critical for informing protection strategies in this vulnerable population. We conducted a longitudinal study of SOT recipients who had recovered from Omicron BA.1 or BA.2 infection, evaluating immune responses to the JN.1 subvariant at 4–6 weeks and 1 year postinfection. Methods: Neutralizing antibodies to JN.1 were measured using a pseudovirus neutralization assay, and JN.1‐specific T‐cell responses were assessed by flow cytometry. Frequencies of bulk T‐cells and innate immune cells, identified via flow cytometry, and their correlation with adaptive responses were also analyzed. Results: At 4–6 weeks, 30% of participants had detectable JN.1‐neutralizing antibodies, rising to 43% at one year, although titers remained low. In contrast, CD4⁺ T‐cell responses were robust and detected in 75%–83% of participants at 4–6 weeks, increasing to 75%–93% by 1 year. CD8⁺ T‐cell responses were observed less frequently. Exploratory correlations between innate and bulk T‐cell subsets with heterologous adaptive immune responses were investigated but did not reveal statistically significant relationships. Conclusion: These findings offer important insights into the durability and breadth of immunity following natural infection in immunocompromised transplant recipients. While heterologous neutralizing antibodies were limited, sustained CD4 ⁺ T‐cell responses may help mitigate severe disease following exposure to JN.1‐derived variants, which continue to dominate the SARS‐CoV‐2 landscape.

Background: There are few in-depth immunogenicity analyses of novel influenza vaccination strategies in high-risk patients with hematological malignancy (HM). Methods: Participants receiving treatment for active HM (multiple myeloma [MM], chronic lymphocytic leukemia [CLL], or non-Hodgkin lymphoma [NHL]) in a randomized controlled trial of 2 doses of adjuvanted quadrivalent inactivated influenza vaccine (QIV) versus 2 doses of standard-dose QIV during 2022 were included. Hemagglutination (HA) inhibition assay and HA probe–specific B-cells were compared at baseline and 1, 2, and 6 months after the first vaccine dose (visits 1–4). A subset underwent ex vivo live virus infection of peripheral blood mononuclear cells at visits 1 and 3 with A/H1N1 and A/H3N2 to assess interferon (IFN) γ–producing CD4+ T cells, CD8+ T cells, natural killer cells, CD161+TRAV1-2+ mucosal-associated invariant T (MAIT)–like T cells and γδ T cells. Results: In total, 62 patients with HM were analyzed (32 in the adjuvanted-dose and 30 in the standard-dose group), 13 (21.0%) with CLL, 24 (38.7%) MM, and 25 (40.3%) with NHL. Participants with MM had higher geometric mean antibody titers (P < .001) and influenza-specific B-cell responses for H1, H3, and B/Victoria at visits 2 and 3 than those with CLL or NHL (P < .05). The total CD19+ B-cell and HA probe–specific B-cell counts were found to significantly predict seroconversion at visits 2 and 3. Overall, with vaccination, there was an increase in the percentage frequency of B/Victoria influenza–specific B-cells (P = .01), IFN-γ–producing CD4+ T cells (P = .01) for A/H1N1 and IFN-γ–producing MAIT-like cells (P = .003) for A/H3N2. Conclusions: Influenza strain–specific cellular responses were detectable following vaccination despite expected B-cell depletion in patients receiving active treatment for HM. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry ACTRN12622000454774.