Anti-CD20 disease modifying therapies decrease the humoral response to COVID-19 mRNA vaccination in patients with multiple sclerosis

Introduction: B-cell depleting (anti-CD20) disease modifying therapies (DMT) for multiple sclerosis (MS) may increase the risk for COVID-19 and worsen clinical outcomes. How these patients respond to mRNA vaccines is not known since immunosuppressed patients were not included in clinical trials. Objective/Aim: To explore the humoral response in MS patients on B-cell depleting therapies to mRNA vaccination against COVID-19. Methods: Immunoglobulin G antibodies to the SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleocapsid protein (N) were measured in MS patients and compared to control participants 3-4 weeks after initial and 3-6 weeks after the second mRNA vaccination. Clinical responses to the vaccination were also collected and compared. Results: After the 2nd vaccine dose, 10/10 controls developed antibodies to RBD, but only 2/10 MS patients on anti-CD20 DMTs (OR 0.014, 95% CI 0.0005 - 0.3328). After the 1st vaccine dose, 6/7 controls had seroconverted while 0/6 seroconverted in the anti- CD20 treated MS patients. Two patients who had COVID-19 on rituximab did not developed antibodies to the nucleocapsid protein but seroconverted to RBD after the 1st vaccination dose. Antibody titers were significantly reduced in the MS patients (p<0.001). No differences in clinical response to the vaccine were observed. T-cell responses are being evaluated and will be presented. Conclusions: Patients with MS on anti-CD20 DMT are less likely to develop antibodies to SARS-CoV-2 RBD and had lower titers after mRNA vaccination. This highlights the importance of better understanding vaccine responsiveness with larger studies and developing better strategies for effective vaccination in MS patients on B-cell depleting therapies.

Constructing an ethical framework for priority allocation of pandemic vaccines.

BACKGROUND: Allocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment. METHODS: Published and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context. FINDINGS: Published and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes. INTERPRETATION: Defining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.

Priority allocation of pandemic influenza vaccines in Australia - Recommendations of 3 community juries.

BACKGROUND: Pandemic planning has historically been oriented to respond to an influenza virus, with vaccination strategy being a key focus. As the current COVID-19 pandemic plays out, the Australian government is closely monitoring progress towards development of SARS-CoV2 vaccines as a definitive intervention. However, as in any pandemic, initial supply will likely be exceeded by demand due to limited manufacturing output. METHODS: We convened community juries in three Australian locations in 2019 to assess public acceptability and perceived legitimacy of influenza pandemic vaccination distribution strategies. Preparatory work included literature reviews on pandemic vaccine allocation strategies and on vaccine allocation ethics, and simulation modelling studies. We assumed vaccine would be provided to predefined priority groups. Jurors were then asked to recommend one of two strategies for distributing remaining early doses of vaccine: directly vaccinate people at higher risk of adverse outcomes from influenza; or indirectly protect the general population by vaccinating primary school students, who are most likely to spread infection. RESULTS: Thirty-four participants of diverse backgrounds and ages were recruited through random digit dialling and topic-blinded social media advertising. Juries heard evidence and arguments supporting different vaccine distribution strategies, and questioned expert presenters. All three community juries supported prioritising school children for influenza vaccination (aiming for indirect protection), one by 10-2 majority and two by consensus. Justifications included that indirect protection benefits more people and is likely to be more publicly acceptable. CONCLUSIONS: In the context of an influenza pandemic, informed citizens were not opposed to prioritising groups at higher risks of adverse outcomes, but if resources and epidemiological conditions allow, achieving population benefits should be a strategic priority. These insights may inform future SARS-CoV-2 vaccination strategies.