There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP) as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1). In this study, a seasonal trivalent VLP vaccine (TVV) formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI) antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV). Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge.

In anticipation of the successful eradication of wild polio virus, alternative vaccination strategies for public-sector markets of low-resource countries are extremely important, but are still under development. Following polio eradication, inactivated polio vaccine (IPV) would be the only polio vaccine available, and would be needed for early childhood immunization for several years, as maintenance of herd immunity will be important for sustaining polio eradication. Low-cost combination vaccines containing IPV could provide reliable and continuous immunization in the post-polio eradication period. Combination vaccines can potentially simplify complex pediatric routine immunization schedules, improve compliance, and reduce costs. Hexavalent vaccines containing Diphtheria (D), Tetanus (T), whole cell pertussis (wP), Hepatitis B (HBV), Haemophilus b (Hib) and the three IPV serotype antigens have been considered as the ultimate combination vaccine for routine immunization. This product review evaluates potential hexavalent vaccine candidates by composition, probable time to market, expected cost of goods, presentation, and technical feasibility and offers suggestions for development of low-cost hexavalent combination vaccines. Because there are significant technical challenges facing wP-based hexavalent vaccine development, this review also discusses other alternative approaches to hexavalent that could also ensure a timely and reliable supply of low-cost IPV based combination vaccines.

SUMMARYThe intradermal inoculation of four badgers with small numbers of Mycobacterium bovis resulted in localized lesions with ulceration which slowly healed by 5 months after inoculation. Lesions of generalized tuberculosis were seen in three badgers, one of which died at 17 months post-inoculation and in the remaining two killed 22 months post-inoculation. In the fourth badger lesions were confined to the draining lymph node of the inoculation site but M. bovis was isolated from the liver. Monthly clinical sampling of faeces, urine, tracheal aspirate and inoculation site exudates detected only the excretion of M. bovis from the inoculation site of one badger. There were marked seasonal variations in body weight but significant weight loss was observed during the second year in all four badgers, particularly prior to death. Four badgers inoculated intratracheally with a similar inoculum of M. bovis and another two control badgers showed no evidence of infection with M. bovis.

HighlightsA wide variety of RSV neutralization assay formats are currently used by the field.This study assessed the current level of agreement between twelve assay formats.Results showed precision was consistently high, whereas agreement varied widely.Results indicated harmonization could be improved with an international standard.Results provided information on samples that may be appropriate for IS development.

SUMMARYOptimal conditions were determined for performing antibody measurements (ELISA), lymphocyte transformation tests and, to some extent, skin tests in badgers. These parameters, together with the bacteriological and pathological studies reported previously (Pritchard et al. 1987), were used to follow the course of intradermal and intratracheal challenge of badgers with bovine tubercle bacilli. Two challenge doses were used for each route of infection and two animals received each dose. None of the four animals challenged by the intratracheal method showed any evidence of infection, suggesting that adult badgers may have some resistance to challenge by this method. All four animals challenged intradermally developed lesion of tuberculosis.Immunologically the disease passed through three phases. There was an early phase in which lymphocyte transformation to whole BCG steadily and significantly increased, and skin tests to tuberculin became positive but there was little change in antibody levels. This was followed by an intermediate phase of variable skin responses, fluctuating lymphocyte transformation and significant increase in antibody levels. The final phase, which was only seen in two animals with extensive disease, was associated with changing skin reactions and falling lymphocyte responses, together with a sudden increase in antibody levels.This paper presents the first formal evidence of cell-mediated immunity to tuberculosis in the badger, which may delay onset and prolong the survival of challenged animals.