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The properties of the alpha-toxins produced by isolates of Clostridium perfringens from the intestine or from soft tissues of man and cattle are compared with those of the alpha-toxin from the type strain NCTC 8237. The alpha toxins are shown to differ in their reactions to a neutralizing monoclonal antibody, although the difference had no effect on the enzymic or toxic properties of the protein. A genetically engineered vaccine derived from the alpha-toxin of the strain NCTC 8237 is also shown to provide protection against alpha-toxins from other strains.

This review article focuses on intranasal immunisation against influenza, although it also encompasses antigen uptake and processing in the nasopharyngeal passages, host defence from influenza and current influenza vaccination practices. Improvement of current vaccination strategies is clearly required; current procedures involve repeated annual injections that sometimes fail to protect the recipient. It is envisaged that nonpercutaneous immunisation would be more attractive to potential vaccinees, thus improving uptake and coverage. As well as satisfying noninvasive criteria, intranasal influenza immunisation has a number of perceived immunological advantages over current procedures. Perhaps one of the greatest attributes of this approach is its potential to evoke the secretion of haemagglutinin-specific IgA antibodies in the upper respiratory tract, the main site of viral infection. Inactivated influenza vaccines have the advantage that they have a long history of good tolerability as injected immunogens, and in this respect are possibly more likely to be licensed than attenuated viruses. Inert influenza vaccines are poor mucosal immunogens, requiring several administrations, or prior immunological priming, in order to engender significant antibody responses. The use of vaccine delivery systems or mucosal adjuvants serves to appreciably improve the immunogenicity of mucosally applied inactivated influenza vaccines. As is the case when they are introduced parenterally, inactivated influenza vaccines are relatively poor stimulators of virus-specific cytotoxic T lymphocyte activity following nasal inoculation. Live attenuated intranasal influenza vaccines are at a far more advanced stage of clinical readiness (phase III versus phase I). With the use of live attenuated vaccines, it is possible to stimulate mucosal and cell-mediated immunological responses of a similar kind to those elicited by natural influenza infection. In children, recombinant live attenuated cold-adapted influenza viruses are well tolerated. Moreover, cold-adapted influenza viruses usually stimulate protective immunity following only a single nasal inoculation. Safety of recombinant live attenuated cold-adapted influenza viruses has also been demonstrated in high risk individuals with cystic fibrosis, asthma, cardiovascular disease and diabetes mellitus. They are not suitable for immunising immunocompromised patients, however, and are poorly efficacious in individuals with pre-existing immunity to strains closely antigenically matched with the recombinant virus. According to the reviewed literature, it is apparent that intranasal administration of vaccine as an aerosol is superior to administration as nose drops. The information reviewed in this paper suggests that nasally administered influenza vaccines could make a substantial impact on the human and economic cost of influenza. [ABSTRACT FROM AUTHOR]

• A novel dual route vaccination using the MERS-CoV RBD sub-unit has been developed. • Murine antisera induced to the RBD protein , were neutralising in vitro. • MERS-CoV susceptibility was induced in naïve mice with Ad5hDPP4. • Passive transfer of anti-RBD sera protected susceptible mice. • Protected mice had a significantly reduced viral titre (P = 0.02) in their lungs. Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo , susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV. [ABSTRACT FROM AUTHOR]

Here, we report a dual-route vaccination approach for plague, able to induce a rapid response involving systemic and mucosal immunity, whilst also providing ease of use in those resource-poor settings most vulnerable to disease outbreaks. This novel vaccine (VypVaxDuo) comprises the recombinant F1 and V proteins in free association. VypVaxDuo has been designed for administration via a sub-cutaneous priming dose followed by a single oral booster dose and has been demonstrated to induce early onset immunity 14 days after the primary immunisation; full protective efficacy against live organism challenge was achieved in Balb/c mice exposed to 2 × 10 4 median lethal doses of Yersinia pestis Co92, by the sub-cutaneous route at 25 days after the oral booster immunisation. This dual-route vaccination effectively induced serum IgG and serum and faecal IgA, specific for F1 and V, which constitute two key virulence factors in Y. pestis , and is therefore suitable for further development to prevent bubonic plague and for evaluation in models of pneumonic plague. This is an essential requirement for control of disease outbreaks in areas of the world endemic for plague and is supported further by the observed exceptional stability of the primary vaccine formulation in vialled form under thermostressed conditions (40 °C for 29 weeks, and 40 °C with 75% relative humidity for 6 weeks), meaning no cold chain for storage or distribution is needed. In clinical use, the injected priming dose would be administered on simple rehydration of the dry powder by means of a dual barrel syringe, with the subsequent single booster dose being provided in an enteric-coated capsule suitable for oral self-administration. [ABSTRACT FROM AUTHOR]