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.