Background
Malaria
is a major global health challenge, and for the elimination and
eradication of this disease, transmission-blocking vaccines (TBVs) are a
priority. Plasmodium falciparum Generative
Cell Specific 1 (PfGCS1), a promising TBV candidate, is essential for
gamete fertilization. The HAP2-GCS1 domain of this antigen as well as
its cd loop could induce antibodies that partially inhibit transmission
of P. falciparum.
Methods
In
the current study, a new synthetic fusion antigen containing cd loop
and HAP2-GCS1 domain (cd-HAP) of PfGCS1 was evaluated as a transmission
blocking vaccine candidate. Initially, the profile of naturally acquired
IgG antibodies to the cd-HAP antigen was analysed in Iranian
individuals infected with P. falciparum,
to confirm that this new fusion protein has the appropriate structure
containing common epitopes with the native form of PfGCS1. Then, the
immunogenicity of cd-HAP was evaluated in BALB/c mice, using different
adjuvant systems such as CpG, MPL, QS-21, and a combination of them
(CMQ). Furthermore, the blocking efficacy of polyclonal antibodies
induced against these formulations was also assessed by oocyst intensity
and infection prevalence in the Standard Membrane Feeding Assay (SMFA).
Results
The naturally acquired antibodies (dominantly IgG1 and IgG3 subclasses) induced in P. falciparum-infected
individuals could recognize the cd-HAP antigen which implies that the
new fusion protein has a proper conformation that mimics the native
structure of PfGCS1. Concerning the immunogenicity of cd-HAP antigen,
the highest IgG levels and titers, by a Th1-type immune profile, and
elevated antibody avidity were induced in mice immunized with the cd-HAP
antigen formulated with a combination of adjuvants (P < 0.0001).
Additionally, cytokine profiling of the immunized mice displayed that a
high level of IFN-γ response, a Th1-type immune response, was produced
by splenocytes from immunized mice that received cd-HAP antigen in
combination with CMQ adjuvants (P < 0.0001).
This formulation of cd-HAP antigen with CMQ adjuvants could reduce
oocyst intensity and infection prevalence by 82%, evidenced by the SMFA
and hold significant implications for future malaria vaccine
development.
Conclusion
Altogether,
the results showed that cd-HAP antigen formulated with a combination of
the adjuvants (CMQ), could be a promising formulation to develop a
PfGCS1-based transmission-blocking vaccine.