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PubMed2002

Blueprint for schistosomiasis vaccine development.

A number of different schistosome antigens are capable of partially protecting experimental animals from challenge infection. More than 100 such antigens have been identified, about 15% of which are strongly protective and deemed promising though they do not reach the level close to sterile immunity seen after vaccination with irradiated cercariae. Studies of human correlate reactions, i.e. serological reactions and cytokine responses to schistosomiasis antigens, in individuals living in areas endemic for schistosomiasis have shown associations between certain antigen-specific immune responses and lack of re-infection over time. This approach was applied in Brazil and Egypt where it was possible to epidemiologically follow cohorts of individuals in endemic areas for extended periods of time correlating infection status with immune responses against a panel of well-researched, highly purified vaccine candidates. The immune correlates found were unique to each antigen and could be either positive or negative, i.e. associated with resistance or with susceptibility to re-infection. However, few antigens were clear-cut in this respect, i.e. the majority of them induced ambiguous responses. For example, a single antigen might have a significant positive correlation when antigen-driven interferon (INF)-gamma production is measured but also show a significant negative correlation with respect to the IgG1 titre induced. These observations suggest that there are desirable, antigen-specific immune responses that would be valuable in a vaccine but they also indicate that there are responses that must be avoided. The insights gained should be useful not only for antigen selection but also for vaccine formulation prior to Phase I/II trials in humans. It would be of great value if similar independent, long-term human correlate studies could also be undertaken in areas endemic for Schistosoma japonicum.

Animals↗
PubMed2005

Protective efficacy in chickens, geese and ducks of an H5N1-inactivated vaccine developed by reverse genetics.

We generated a high-growth H5N1/PR8 virus by plasmid-based reverse genetics. The virulence associated multiple basic amino acids of the HA gene were removed, and the resulting virus is attenuated for chickens and chicken eggs. A formalin-inactivated oil-emulsion vaccine was prepared from this virus. When SPF chickens were inoculated with 0.3 ml of the vaccine, the hemagglutinin-inhibition (HI) antibody became detectable at 1 week post-vaccination (p.v.) and reached a peak of 10log2 at 6 weeks p.v. then slowly declined to 4log2 at 43 weeks p.v. Challenge studies performed at 2, 3 and 43 weeks p.v. indicated that all of the chickens were completely protected from disease signs and death. Ducks and geese were completely protected from highly pathogenic H5N1 virus challenge 3 weeks p.v. The duration of protective immunity in ducks and geese was investigated by detecting the HI antibody of the field vaccinated birds, and the results indicated that 3 doses of the vaccine inoculation in geese could induce a 34 weeks protection, while 2 doses induced more than 52 weeks protection in ducks. We first reported that an oil-emulsion inactivated vaccine derived from a high-growth H5N1 vaccine induced approximately 10 months of protective immunity in chickens and demonstrated that the oil-emulsion inactivated avian influenza vaccine is immunogenic for geese and ducks. These results provide useful information for the application of vaccines to the control of H5N1 avian influenza in poultry, including chickens and domestic waterfowl.

Animals↗
PubMed1998

Schistosomiasis vaccine development: progress and prospects.

The undisputed, worldwide success of chemotherapy notwithstanding, schistosomiasis continues to defy control efforts in as much rapid reinfection demands repeated treatment, sometimes as often as once a year. There is thus a need for a complementary tool with effect for the longer term, notably a vaccine. International efforts in this direction have been ongoing for several decades but, until the recombinant DNA techniques were introduced, antigen production remained an insurmountable bottleneck. Although animal experiments have been highly productive and are still much needed, they probably do not reflect the human situation adequately and real progress can not be expected until more is known about human immune responses to schistosome infection. It is well-known that irradiated cercariae consistently produce high levels of protection in experimental animals but, for various reasons, this proof of principle cannot be directly exploited. Research has instead been focussed on the identification and testing of specific schistosome antigens. This work has been quite successful and is already at the stage where clinical trials are called for. Preliminary results from coordinated in vitro laboratory and field epidemiological studies regarding the protective potential of several antigens support the initiation of such trials. A series of meetings, organized earlier this year in Cairo, Egypt, reviewed recent progress, selected suitable vaccine candidates and made firm recommendations for future action including pledging support for large-scale production according to good manufacturing practice (GMP) and Phase I trials. Scientists at the American Centers for Disease Control and Prevention (CDC) have drawn up a detailed research plan. The major financial support will come from USAID, Cairo, which has established a scientific advisory group of Egyptian scientists and representatives from current and previous international donors such as WHO, NIAID, the European Union and the Edna McConnell Clark Foundation.

Animals↗
PubMedDate not supplied

Adhesins as targets for vaccine development.

Blocking the primary stages of infection, namely bacterial attachment to host cell receptors and colonization of the mucosal surface, may be the most effective strategy to prevent bacterial infections. Bacterial attachment usually involves an interaction between a bacterial surface protein called an adhesin and the host cell receptor. Recent preclinical vaccine studies with the FimH adhesin (derived from uropathogenic Escherichia coli) have confirmed that antibodies elicited against an adhesin can impede colonization, block infection, and prevent disease. The studies indicate that prophylactic vaccination with adhesins can block bacterial infections. With recent advances in the identification, characterization, and isolation of other adhesins, similar approaches are being explored to prevent infections, from otitis media and dental caries to pneumonia and sepsis.

Adhesins, Bacterial↗