Examples of vaccine-induced enhancement of susceptibility to virus infection or of aberrant viral pathogenesis have been documented for infections by members of different virus families. Several mechanisms, many of which still are poorly understood, are at the basis of this phenomenon. Vaccine development for lentivirus infections in general, and for HIV/AIDS in particular, has been little successful. Certain experimental lentiviral vaccines even proved to be counterproductive: they rendered vaccinated subjects more susceptible to infection rather than protecting them. For vaccine-induced enhanced susceptibility to infection with certain viruses like feline coronavirus, Dengue virus, and feline immunodeficiency virus, it has been shown that antibody-dependent enhancement (ADE) plays an important role. Other mechanisms may, either in the absence of or in combination with ADE, be involved. Consequently, vaccine-induced enhancement has been a major stumble block in the development of certain flavi-, corona-, paramyxo-, and lentivirus vaccines. Also recent failures in the development of a vaccine against HIV may at least in part be attributed to induction of enhanced susceptibility to infection. There may well be a delicate balance between the induction of protective immunity on the one hand and the induction of enhanced susceptibility on the other. The present paper reviews the currently known mechanisms of vaccine-induced enhancement of susceptibility to virus infection or of aberrant viral pathogenesis.

Specific pathogen free (SPF) domestic cats were inoculated with tissue homogenate obtained from a Chinese leopard (Panthera pardusjaponensis) that had died in a North American zoo from a natural infection with canine distemper virus (CDV). The cats developed a transient cell-associated CDV viraemia along with pronounced lymphopenia but did not show any clinical symptoms. Plasma neutralizing-antibody titres against the homologous CDV (A92-27/4, isolated from the Chinese leopard) were consistently higher than against the CDV vaccine strain 'Bussell'. The Chinese leopard CDV isolate showed in vitro biological properties reminiscent of virulent, wild-type CDV strains. Sequence analysis of the H gene of two large felid CDV isolates from the USA (A92-27/4 and A92-6) revealed up to 10 % amino acid changes including up to four additional potential N-linked glycosylation sites in the extracytoplasmic domain as compared to CDV vaccine strains. Phylogenetic analysis was performed using the entire coding region of the H gene and a 388 bp fragment of the P gene of several morbillivirus species. Evidence was obtained that recent CDV isolates from different species in the United States (including isolates from large felids), Europe and Africa are significantly distinct from CDV vaccine strains. All wild-type CDV isolates analysed clustered according to geographical distribution rather than to host species origin. By sequence analysis a CDV epizootic among large felids in a Californian safari park was linked to a virus which most likely originated from feral non-felid carnivores.

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Combined transvaginal/transanal rectocele repair was performed in series of 89 consecutive women (mean age 55, range 35-81 years) with obstructed defecation due to a rectocele with a depth of more than 3 cm. The impact of this procedure on anal sphincter pressure and continence status was evaluated prospectively. Anorectal manometry was carried out before and after surgery (at 3, 6, 12, and 24 months). The following measurements were performed: maximal anal resting pressure (MARP), maximal anal squeeze pressure (MASP), and rectal sensory perception including first initial sensation, urge to defecate, and maximum tolerable volumes (MTV). The outcome was successful in 71% of patients with respect to symptoms such as the need for straining at defecation, manual assistance, feelings of incomplete evacuation, sense of rectal fullness, constipation, abdominal pain, and the use of laxatives. However, after rectocele repair seven patients experienced deterioration in fecal continence, and dyspareunia developed in 41% of the sexually active patients. Manometric studies revealed a significant decline in mean of 18% of MARP and 16% of MASP. In contrast to MASP, MARP gradually improved during the follow-up period. Distending volumes required for initial sensation and urge to defecate did not change after the procedure. MTV values were significantly lower 3 and 6 months after rectocele repair than those before and 24 months after surgery. MARP and MASP values after surgery did not differ between patients with impaired and those with normal continence. In conclusion, transvaginal/transanal rectocele repair is beneficial for patients with obstructed defecation; however, care should be taken in sexually active patients, and patients at risk of developing fecal incontinence.

Cats were immunized three times with different recombinant feline immunodeficiency virus (FIV) candidate vaccines. Recombinant vaccinia virus (rVV)-expressed envelope glycoprotein with (vGR657) or without (vGR657x15) the cleavage site and an FIV envelope bacterial fusion protein (␤-Galactosidase-Env) were incorporated into immune-stimulating complexes or adjuvanted with Quil A. Although all immunized cats developed antibodies against the envelope protein, only the cats vaccinated with the rVV-expressed envelope glycoproteins developed antibodies which neutralized FIV infection of Crandell feline kidney cells. These antibodies failed to neutralize infection of thymocytes with a molecularly cloned homologous FIV. After the third immunization the cats were challenged with homologous FIV. Two weeks after challenge the cellassociated viral load proved to be significantly higher in the cats immunized with vGR657 and vGR657x15 than in the other cats. The cats immunized with vGR657 and vGR657x15 also developed antibodies against the Gag proteins more rapidly than the cats immunized with ␤-Galactosidase-Env or the control cats. This suggested that immunization with rVV-expressed glycoprotein of FIV results in enhanced infectivity of FIV. It was shown that the observed enhancement could be transferred to naive cats with plasma collected at the day of challenge.