Chronic helminth infection does not impair immune response to malaria transmission blocking vaccine Pfs230D1M-EPA/Alhydrogel® in mice

Authors: COELHO, CAMILA - Nih, National Institutes Of Allergy And Infectious Diseases; GAZZINELLI-GUIMARAES, PEDRO - National Institutes Of Health (NIH); HOWARD, JENNINER - Nih, National Institutes Of Allergy And Infectious Diseases; BARNAFO, EMMA - Nih, National Institutes Of Allergy And Infectious Diseases; ALANI, NADA - Nih, National Institutes Of Allergy And Infectious Diseases; MURATOVA, OLGA - Nih, National Institutes Of Allergy And Infectious Diseases; MCCORMACK, ASHLEY - Nih, National Institutes Of Allergy And Infectious Diseases; KELNHOFER, EMILY - Nih, National Institutes Of Allergy And Infectious Diseases; Urban, Joseph; NARUM, DAVID - Nih, National Institutes Of Allergy And Infectious Diseases; ANDERSON, CHARLES - Nih, National Institutes Of Allergy And Infectious Diseases; LANGHORNE, JEAN - The Francis Crick Institute; NUTMAN, THOMAS - National Institutes Of Health (NIH); DUFFY, PATRICK - Nih, National Institutes Of Allergy And Infectious Diseases

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2019
Publication Date: 2/14/2019
Citation: Coelho, C.H., Gazzinelli-Guimaraes, P.H., Howard, J., Barnafo, E., Alani, N.A., Muratova, O., Mccormack, A., Kelnhofer, E., Urban Jr, J.F., Narum, D., Anderson, C., Langhorne, J., Nutman, T.B., Duffy, P.E. 2019. Chronic helminth infection does not impair immune response to malaria transmission blocking vaccine Pfs230D1M-EPA/Alhydrogel® in mice. Scientific Reports. 37(8):1038-1045. https://doi.org/10.1016/j.vaccine.2019.01.027.
DOI: https://doi.org/10.1016/j.vaccine.2019.01.027

Interpretive Summary: Infection of both livestock and humans with parasitic worms causes a modulation of the immune system as the worm attempts to establish in the host without activating immunity that could expel the worm. A very common condition is where humans are exposed to both malaria and worm parasites. Modern vaccines against malaria are increasingly being developed for humans but there is concern that the likely infection of these subjects with worms would reduce the efficacy of the vaccination. A mouse model was developed to experimentally evaluate if worm infection could reduce the effectiveness of a vaccine that is in clinical trials in humans against malaria. The results showed no significant effect on the type of immune response that was induced by the vaccination and, most importantly, that there was no reduction in the level of protection against an infection with malaria in the immunized mice. These studies add a level of confidence that testing of the malaria vaccine in humans that are likely to be infected with worms will not adversely effect vaccine efficacy. The work is important to both research and clinical scientists interested in the health of both livestock and humans exposed to parasitic infection and the application of vaccines to control infection.

Technical Abstract: Malaria transmission blocking vaccines (TBV) are innovative approaches that aim to induce immunity in humans against Plasmodium during mosquito stage, neutralizing the capacity of the infected vectors to transmit malaria. Pfs230D1M-EPA/Alhydrogel®, a promising protein-protein conjugate malaria TBV, is currently being tested in human clinical trials in areas where P. falciparum malaria is coendemic with helminth parasites. Helminths are complex metazoans that share the master capacity to downregulate the host immune response towards themselves and also to bystander antigens, including vaccines. However, it is not known whether the activity of a protein-based malaria TBV may be affected by a chronic helminth infection. Methods: Using an experimental murine model for a chronic helminth infection (Heligmosomoides polygyrus bakeri - Hpb), we evaluated whether prior infection alters the activity of Pfs230D1M-EPA/Alhydrogel® TBV in mice. Results: After establishment of a chronic infection, characterized by a marked increase of parasite antigen-specific IgG1, IgA and IgE antibody responses, concomitant with an increase of systemic IL-10, IL-5 and IL-6 levels, the Hpb-infected mice were immunized with Pfs230D1M-EPA/Alhydrogel® and the vaccine-specific immune response was compared with that in non-infected immunized mice. TBV immunizations induced an elevated vaccine specific-antibody response, however Pfs230 specific-IgG levels were similar between infected and uninfected mice at days 15, 25 and 35 post-vaccination. Absolute numbers of Pfs230-activated B cells generated in response to the vaccine were also similar among the vaccinated groups. Finally, vaccine efficacy assessed by reduction of oocyst number in P. falciparum infected mosquitoes was similar between Hpb-infected and immunized mice with non-infected immunized mice. Conclusion:Pfs230D1M-EPA/Alhydrogel® efficacy is not impaired by a chronic helminth infection in mice.