Effectiveness of tixagevimab/cilgavimab (Evusheld) in antiCD20­treated patients with multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: AntiCD20 therapy, such as rituximab, ocrelizumab, or ofatumumab, effectively treats patients with multiple sclerosis (pwMS) or neuromyelitis optica spectrum disorder (pwNMOSD) but negatively affects the humoral immune response to COVID-19 vaccination. One strategy to protect these patients is using tixagevimab/cilgavimab (T/C) as pre-exposure prophylaxis. This study aimed to evaluate the effect of T/C on the incidence of COVID-19 in pwMS and pwNMOSD. METHODS: Data in this observational cohort study were collected in two Czech MS centres through ReMuS registry between March 1, 2020 and December 31, 2022. Adult pwMS and pwNMOSD who were (1) treated with antiCD20 therapy at least six months before T/C administration, or at least from February 1, 2022 in the control group; (2) were already on antiCD20 therapy at the time of vaccination or COVID-19 infection; and (3) were on antiCD20 therapy at least 100 days after T/C, or at least 90 days after August 1, 2022 in the control group, were included. Analysis was performed using frequency-based (propensity score matching) and Bayesian statistical methods (informative and non-informative priors). RESULTS: Using propensity score matching 1:1, 47 patients who received T/C (mean age 45.7 years, median disease duration 12.5 years) were matched with those who did not receive T/C (n = 341; mean age 46.6 years, median disease duration 11.4 years) based on age, MS/NMOSD duration, and number of vaccine doses. None of the T/C patients and three in the control matched group, developed COVID-19 between 10 and 100 days after receiving T/C, August 1, 2022, respectively. The frequency of COVID-19 was not significantly different between groups (p = 0.242). Due to the low number of patients, a Bayesian analysis was also added. Using a non-informative Bayesian prior, the median relative risk of COVID-19 after T/C was 7.6 % (95 % CrI 0.02-115.9 %). The posterior probability of risk difference lower than zero was 96.4 %. Using an informative prior (based on the registration study of Evusheld), the median relative risk of COVID-19 after T/C was 20.2 % (95 % CI 8.4-43.8 %). The posterior probability of the risk difference lower than zero was 100 %. CONCLUSION: This work highlights the possible good efficacy of T/C in antiCD20-treated pwMS and pwNMSOD. Based on Bayesian analysis with an informative prior, the T/C group's risk of COVID-19 infection was approximately 20.2 % of the control group's risk. However, given the low frequency of COVID-19, the results of this pilot analysis must be interpreted with caution.

Specificity of anti-saliva immune response in mice repeatedly bitten by Phlebotomus sergenti.

Sand flies are bloodsucking insects transmitting parasites of genus Leishmania, the causative agents of diseases in humans and dogs. Experimental hosts repeatedly exposed to sand fly saliva can control Leishmania infection. Cell-mediated anti-saliva immune response is most likely responsible for this protective effect; however, there is no study so far concerning its antigenic specificity towards different sand fly vectors. In this study, splenocytes from BALB/c mice repeatedly exposed to the bites of Phlebotomus sergenti were challenged ex vivo with salivary gland homogenates from three different sand fly vectors -P. sergenti, P. papatasi, or P. arabicus. Mice bitten by P. sergenti had higher proliferative response to homologous antigen than splenocytes from naive mice. Splenocytes from P. sergenti bitten mice as well as anti-P. sergenti antibodies partially cross-reacted with P. papatasi saliva. In contrast, no cross-reactivity was found with P. arabicus saliva. Our data indicate that both arms of the immune system, cellular and humoral, react in a species-specific manner. Therefore, the presence of antibodies against salivary components of a certain species indicates the specificity of cell-mediated immune response as well. The data suggest that unique transmission-blocking vaccine would be required for each vector -Leishmania combination.