A step forward in the journey towards hookworm vaccines

• Published in: The Lancet infectious diseases 2024-07, Vol.24 (7), p.673-674
• Main Authors: Keiser, Jennifer, Bouchery, Tiffany
• Format: Article
• Language: English
• Subjects: Ancylostomatoidea - immunology; Anemia; Animal models; Animals; Antibodies; Antibody response; Antigens; Combined vaccines; Drug dosages; Drugs; Effectiveness; Exposure; Hookworm Infections - prevention & control; Humans; Immunological memory; Immunology; Immunomodulation; Immunosuppressive agents; Infections; Lymphocytes; Lymphocytes T; Memory cells; Mucosa; Parasites; Public health; Vaccines; Vaccines - immunology
• ISSN: 1473-3099; 1474-4457; 1474-4457
• DOI: 10.1016/S1473-3099(24)00145-2

Soil-transmitted helminth infections, comprising Ascaris lumbricoides, Trichuris trichiura, and the two hookworm species Ancylostoma duodenale and Necator americanus, are responsible for an immense burden on public health.1 For decades, large-scale distribution of anthelminthic drugs has been the mainstay infection control measure, yet there are a scant number of drugs with only moderate efficacy available,2 and the intervention is not sustainable due to rapid post-treatment re-infection. Results will then have to be validated in CHHI studies in endemic areas, notably to discover whether the vaccine's efficacy is not affected by previous exposure to hookworms, nor decreased.5 Previous trials of a combined N americanus Na-GST-1 and Na-APR-1(M74) vaccine in an adult Gabonese population showed that experienced memory T cells up-regulated CTA-L4, an inhibitory molecule, potentially affecting antibody response efficacy,7 highlighting that circumventing hookworm immunomodulation might be required for designing an efficient vaccine against hookworms.8 Finding the best antigens against hookworms is a prerequisite in bringing hookworm vaccines to endemic countries, but future research will also have to refine the best delivery for such a vaccine. The optimal route of delivery for a soil-transmitted helminth vaccine may well be mucosal, as soil-transmitted helminth animal models have shown that protective immune responses do take place in mucosal environments,4 and recent discoveries in the field of BCG have emphasised the importance of delivery route.9 Animal models could provide a wealth of information on this topic, and the naturalisation of laboratory mice10 (ie, allowing mice to be exposed to a variety of pathogen exposures to better mimic human complex exposure) could be introduced as a translational step to accelerate vaccine design before testing in CHHI studies.