ABSTRACT
Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5-7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.govNCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4-5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3-1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9-1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8-4.0); none deemed vaccine related. Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5-7 months was safe and not associated with higher rates of reactogenicity than placebo. Funding: Innovation Fund Denmark.
ABSTRACT
A 63-year-old male with metastatic non-small cell lung cancer developed longitudinal extensive transverse myelitis (LETM) following two cycles of Pembrolizumab, an immune checkpoint inhibitor (ICI) targeting the programmed cell death receptor 1 (PD-1). Magnetic resonance imaging (MRI) showed centromedullary contrast enhancement at several levels, cerebrospinal fluid (CSF) cytology showed lymphocytic pleocytosis, and indirect immunofluorescence assay (IFA) on the primate cerebellum, pancreas, and intestine revealed strong binding of neuronal autoantibodies to unknown antigens. CSF C-X-C motif ligand 13 (CXCL13) was elevated. The patient was treated with plasma exchange (PEX) and intravenous (i.v.) methylprednisolone (MP) 1 g/day for 5 days followed by oral (p.o.) MP 100 mg/day for 10 days with clinical and radiological response. However, after discontinuation of MP, LETM relapsed and the patient developed paralytic ileus presumably due to autoimmune enteropathy and suffered a fatal gastrointestinal sepsis. Findings of novel neuronal autoantibodies and highly elevated CXCL13 in CSF suggest that the severe neurological immune-related adverse event (nirAE) was B-cell mediated contrary to the commonly assumed ICI-induced T-cell toxicity. An individual evaluation of the underlying pathophysiology behind rare nirAEs is essential for choosing treatment regimens and securing optimal outcome.
