Immunoinformatic Design and Immunoprotective Effect of an mCTA1- and Smp145-Based Vaccine Against Naegleria fowleri.

Naegleria fowleri is the etiological agent of primary amoebic meningoencephalitis (PAM), a lethal disease with a 97% mortality rate in humans. Currently, there is no vaccine that confers protection against N. fowleri. Recently, we reported that the synthetic membrane peptide (Smp145) was considered as a vaccine candidate, since it induced 60% protection in mice immunised and challenged with N. fowleri. The objective was to design in silico a vaccine based on the A1 domain of cholera toxin (CT), coupled to the Smp145 peptide of N. fowleri, and to evaluate its protective effect in a murine model of PAM. A bioinformatic design was performed with the Ser61Phe mutation in the active site of the A1 domain of CT (mCTA1), linked through a glycine linker to Smp145. Intraperitoneal immunisation with mCTA1-Smp145, followed by challenge with a lethal dose of N. fowleri, resulted in 60% protection, confirming its protective capacity as the most relevant finding. Furthermore, increased levels of IgA and IgG were observed in sera and nasal washes, which recognised antigenic bands of mCTA1-Smp145 and total extracts of N. fowleri. Overall, we propose mCTA1-Smp145 as a potential vaccine against N. fowleri, highlighting that its protective effect constitutes the main support for this proposal.