A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A.

Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) consists of (1 → 6)-2-acetamido-2-deoxy-α-D-mannopyranosyl phosphate repeating units, O-acetylated at position C3 or C4. Glycomimetics appear attractive to overcome the CPS intrinsic lability in physiological media, due to cleavage of the phosphodiester bridge, and to develop a stable vaccine with longer shelf life in liquid formulation. Here, we generate a series of non-acetylated carbaMenA oligomers which are proven more stable than the CPS. An octamer (DP8) inhibits the binding of a MenA specific bactericidal mAb and polyclonal serum to the CPS, and is selected for further in vivo testing. However, its CRM197 conjugate raises murine antibodies towards the non-acetylated CPS backbone, but not the natural acetylated form. Accordingly, random O-acetylation of the DP8 is performed, resulting in a structure (Ac-carbaMenA) showing improved inhibition of anti-MenA CPS antibody binding and, after conjugation to CRM197, eliciting anti-MenA protective murine antibodies, comparably to the vaccine benchmark.

Increasing isolations of Neisseria meningitides serogroup A from blood and cerebrospinal fluid in Dhaka, Bangladesh, 1999-2006.

During 1999-2006, 156 isolates of Neisseria meningitidis grew from culture of blood or cerebrospinal fluid at International Centre for Diarrhoeal Disease Research, Bangladesh, in Dhaka, Bangladesh. Serogroup A was the most prevalent strain (97.7%); the rest were serogroup B (2.3%). Most cases of invasive meningococcal disease (88.5%) were identified in 2002-2004 and most (87.5%) occurred in children, teenagers, and young adults, which reflected a community-wide increase in meningococcal disease incidence during this period, which was not recognized previously. All isolates were susceptible to penicillin, ampicillin, chloramphenicol, ciprofloxacin, and ceftriaxone. Cotrimoxazole resistance steadily increased from 50% to 100% during 2002-2006. Resistance to azithromycin emerged in 2002 (5%), increased to 31% in 2004, but isolates in 2005-2006 were susceptible. Information from broader hospital settings and population-based data would precisely assess trends and impact to define strategies for optimal prevention and empiric therapy.

Clinical profile of group A meningococcal outbreak in Delhi.

We present a retrospective analysis of clinical profile of 100 children admitted to a Government hospital at Delhi between April 2005 and December 2006 with group A meningococcal infection. Maximum children presented in late winter and spring. Younger children were less affected (5% children < 1 year). Fever (86%), vomiting (64%) and rash (63%) were the most common presenting symptoms. All children presented within 5 days of onset of symptoms and 52% within 24 hours. 67 % children had meningococcal meningitis; 20% had meningococcemia; and 13% had both. Overall mortality was 17%. Altered sensorium and shock at presentation significantly increased the mortality. All culture positive cases had group A Neisseria meningitides. All meningococcal isolates were sensitive to penicillin/ampicillin, ciprofloxacin, ceftriaxone, chloramphenicol and erythromycin except, one each resistant to ampicillin and erythromycin.

Ciprofloxacin-resistant Neisseria meningitidis, Delhi, India.

Decreased susceptibility of Neisseria meningitidis isolates to ciprofloxacin emerged from an outbreak in Delhi, India. Results of antimicrobial susceptibility testing of the meningococcal isolates to ciprofloxacin and further sequencing of DNA gyrase A quinolone-resistance-determining region confirmed the emergence of ciprofloxacin resistance in the outbreak.