Safety of neuraminidase inhibitors for influenza

Neuraminidase inhibitors, oseltamivir and zanamivir, are used for the treatment of, and protection from, influenza. The safety of these compounds has been assessed in systematic reviews. However, the data presented are somewhat limited by the paucity of good quality adverse event data available. The majority of safety outcomes are based on evidence from just one or two randomised controlled trials. The results of the systematic reviews suggest that neuraminidase inhibitors have a reasonable side effect and adverse effect profile if they are to be used to treat or protect patients against a life-threatening disease. However, if these compounds are to be prescribed in situations in which avoidance of inconvenience or minor discomfort is hoped for, then the balance of harms to benefits will be more difficult to judge.

Method for the synthesis of highly pure vaccines using the lipid core peptide system

Traditional vaccines consisting of whole attenuated microorganisms, killed microorganisms, or microbial components, administered with an adjuvant (e.g. alum), have been proved to be extremely successful. However, to develop new vaccines, or to improve upon current vaccines, new vaccine development techniques are required. Peptide vaccines offer the capacity to administer only the minimal microbial components necessary to elicit appropriate immune responses, minimizing the risk of vaccination associated adverse effects, and focusing the immune response toward important antigens. Peptide vaccines, however, are generally poorly immunogenic, necessitating administration with powerful, and potentially toxic adjuvants. The attachment of lipids to peptide antigens has been demonstrated as a potentially safe method for adjuvanting peptide epitopes. The lipid core peptide (LCP) system, which incorporates a lipidic adjuvant, carrier, and peptide epitopes into a single molecular entity, has been demonstrated to boost immunogenicity of attached peptide epitopes without the need for additional adjuvants. The synthesis of LCP systems normally yields a product that cannot be purified to homogeneity. The current study describes the development of methods for the synthesis of highly pure LCP analogs using native chemical ligation. Because of the highly lipophilic nature of the LCP lipid adjuvant, difficulties (e.g. poor solubility) were experienced with the ligation reactions. The addition of organic solvents to the ligation buffer solubilized lipidic species, but did not result in successful ligation reactions. In comparison, the addition of approximately 1% (w/v) sodium dodecyl sulfate (SDS) proved successful, enabling the synthesis of two highly pure, tri-epitopic Streptococcus pyogenes LCP analogs. Subcutaneous immunization of B10.BR (H-2(k)) mice with one of these vaccines, without the addition of any adjuvant, elicited high levels of systemic IgG antibodies against each of the incorporated peptides. Copyright (c) 2006 European Peptide Society and John Wiley & Sons, Ltd.

Chapter 8 HPV vaccines

Vaccines to prevent infection with high-risk human papillomaviruses (HPV) will help protect women against cervical cancer, and some are likely to be available within the next year. One vaccine, a quadrivalent vaccine against HPV types 6, 11, 16 and 18 and known as Garadsil ©(Merck &Co., Inc), was approved by the Federal Drug Administration (FDA) for the prevention of cervical cancer, cervical cancer precursors and vulval and vaginal cancer precursors associated with HPV 16 and 18 in June 2006. In addition, the vaccine has been approved for the prevention of genital warts and low grade cervical lesions e.g. cervical intraepithelial neoplasia1. The main vaccines components are recombinant viral capsid proteins assembled into virus-like particles and alum-based adjuvants. If given before HPV infection, the vaccines, which induce HPV type-specific, virus-neutralizing antibodies, have proven safe and highly effective at preventing HPV infection and its clinical consequences, including high-grade cervical lesions. Their use should not immediately alter existing screening programs for cervical cancer, however. Because they incorporate only the 2 HPV types most commonly associated with cervical cancer (HPV-16 and HPV-18), they can only prevent about 70% of cervical cancers. Vaccines to treat existing HPV infection are under development but are unlikely to become clinically available in the near future.

Successful treatment of post-influenza pseudomembranous necrotising bronchial aspergillosis with liposomal amphotericin, inhaled amphotericin B, gamma interferon and GM-CSF

A case of aspergillus tracheobronchitis following influenza A infection in an immunocompetent 35 year old woman is described that required prolonged mechanical ventilation for airways obstruction. Treatment included liposomal amphotericin, inhaled amphotericin, gamma interferon and GM-CSF. Liposomal amphotericin therapy was associated with reversible hepatosplenomegaly. Inhaled corticosteroids with continued antifungal therapy were used for the management of severe recurrent airway obstruction. After a prolonged course of treatment she survived with fixed airways obstruction unresponsive to corticosteroids.