PEV7 - Pevion Biotech AG

2
Yeast fungus Candida albicans
PEV7 vaccine with recombinant
protein antigen presented on the
surface of virosomes
V A C C I N E P R O F I L E
PEV7 is a state-of-the-art therapeutic vaccine against recurrent vulvovaginal
candidiasis (RVVC) caused by the pathogenic form of Candida albicans
indicated for women with a history of RVVC. The vaccine candidate uses a
proprietary, recombinant Sap2 protein antigen, one of the main Candida
albicans virulence factors, presented on the surface of virosomes. PEV7 is being
developed in two galenic forms, one for standard intramuscular injection and
one for intravaginal application (capsules).
R A T I O N A L E F O R V A C C I N E D E S I G N
Immunological mechanisms functioning at the vaginal mucosa are still a topic
of intense research and much of what is known comes from animal rather than
human data. Candida-specific cell-mediated immunity has for a long time been
considered the major host defense mechanism against mucosal candida
infections. However, recent studies have demonstrated the important role of
humoral immunity in protection against mucosal candidiasis. More generally,
mucosal antibodies, both secreted IgA and transudated IgG, are highly
important for immunity against pathogens that enter via mucosal surfaces,
since they can act early on during the infection cycle. In the genital tract, IgA
and IgG are equally important and according to preclinical observations, anticandida
IgA and IgG antibodies bind to candida species, thereby reducing
their ability to adhere to epithelial cells and thus preventing the tissue
penetration phase. Based on this knowledge, the goal of Pevion’s candida
vaccine is to elicit a strong protective antibody response that prevents
recurrence.
Recent research also demonstrated that mucosal immunization or a
combination of intramuscular and mucosal immunization can be more efficient
than intramuscular immunization alone. This concept is currently being clinically
validated by two virosomal vaccines. Notably, the candida vaccine PEV7 and
furthermore a HIV vaccine of Pevion’s licensee Mymetics, which demonstrated
good safety and immunogenicity in human at both low and high dose. For the
candida vaccine, Pevion has developed a formulation for intravaginal mucosal
application (capsules), which would also be more convenient for the patient.
Pevion exclusively in-licensed a recombinant Sap2 protein antigen from the
Istituto Superiore di Sanità in Rome (Italy). Sap2 has been identified as a main
virulence factor and represents a prime vaccine target. The use of a protein
antigen requires a suitable carrier and adjuvant system, and Pevion’s virosome
technology is the optimal choice for this purpose.
P R E C L I N I C A L R E S U L T S
In summary, key findings from animal studies are as follows:
Rats immunized with PEV7 showed a rapid fungal clearance from vaginal
fluid, when challenged with pathogenic Candida albicans, in particular during
the first days, which are the most burdening in terms of disease symptoms
The protective efficacy of PEV7 was dose-dependent
PEV7 elicited robust antibody levels in vaginal fluid of both IgA and IgG
specific for the native target protein
Intranasal, sublingual, and vaginal routes of administration resulted in
comparable protection
Toxicity studies in rats, rabbits, and minipigs showed no abnormalities and
merely very mild local irritation
Preclinical studies clearly demonstrated that intravaginal administration of
PEV7 generated a solid immune response to the native antigen target in the
vagina and at the same time leads to very rapid elimination of candida
infection. Both antibody isotypes, IgA and IgG, which are essential for mucosal
immunity, were present in vaginal fluid of immunized animals. Furthermore, it
has been proven that the virosome-based component enhances both
immunogenicity and the protective effect of the antigen.