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Abstract. Non-Axiomatic Logic (NAL) is designed for intelligent reasoning, and can be used in a system that has insufficient knowledge and resources with respect to the problems to be solved. This paper reports the result of a case study that applies NAL in medical diagnostics, and the logic is compared with binary logic and probability theory.

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Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 μg of H1ssF once ( n  = 5) or 60 μg of H1ssF twice ( n  = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-μg dose participants received the boost, whereas 11 (23%) boost vaccinations were missed because of public health restrictions in the early stages of the COVID-19 pandemic. The primary objective of this trial was to evaluate the safety and tolerability of H1ssF, and the secondary objective was to evaluate antibody responses after vaccination. H1ssF was safe and well tolerated, with mild solicited local and systemic reactogenicity. The most common symptoms included pain or tenderness at the injection site ( n  = 10, 19%), headache ( n  = 10, 19%), and malaise ( n  = 6, 12%). We found that H1ssF elicited cross-reactive neutralizing antibodies against the conserved HA stem of group 1 influenza viruses, despite previous H1 subtype head-specific immunity. These responses were durable, with neutralizing antibodies observed more than 1 year after vaccination. Our results support this platform as a step forward in the development of a universal influenza vaccine.

Purpose of reviewAnti-HIV-1 broadly neutralizing antibodies (bNAbs) are promising agents in the fight against the AIDS epidemic. Multiple bNAbs have been already evaluated in clinical trials with encouraging results. This review discusses the use of bNAbs for the prevention and treatment of HIV-1 infection, focusing on manufactured products that have been evaluated in clinical settings. Recent findingsMore than 17 bNAbs have been evaluated for safety and pharmacokinetics in humans. The vast majority presented a well tolerated profile and were generally well tolerated. Serum half-life varied from 12 to 73.5 days and can be improved by the addition of mutations to the Fc regions. Results from the antibodymediated prevention (AMP) study show that VRC01, a CD4-binding-site bNAb, was effective at preventing the acquisition of sensitive HIV-1 strains but did not prevent the acquisition of strains whose in vitro sensitivity to the antibody had an IC 80 of more than 1 mg/ml. New bNAb combinations to improve coverage are currently being evaluated.

Vector borne diseases have been associated with a number of autoimmune diseases. In this case we report a 73 year old woman initially diagnosed with lyme disease who subsequently developed guillain-barre syndrome (GBS). Her relevant clinical presentation included protean symptoms of numbness and progressive weakness in her legs for three weeks prior to consultation by the neurology service. A lyme ELISA and confirmatory Western Blot testing were unequivocally positive. A clinical diagnosis of CNS lyme disease was made. Additional clinical evaluation included: electrophysiological testing, which demonstrated significant polyneuropathy consistent with demyelinating pathology. A lumbar puncture with cerebral spinal fluid analysis revealed a non-reactive VDRL, negative lyme DNA PCR, positive lyme IgG antibody and an elevated protein-elevated albumin with normal white count. Upon further clinical deliberation this constellation of signs and symptoms was determined to be more consistent with a diagnosis of GBS rather than CNS lyme disease. Initiation of medical therapy included IVIG (intravenous immunoglobulin) and parenteral ceftriaxone. This case may report an additional vector of disease in patients presenting with clinical signs and symptoms of GBS.