Cross-reactivity of R48/45, a Recombinant Protein, with Sera from Endemic Areas of Africa

Overview

Journal bioRxiv

Date 2024 Apr 25

PMID 38659832

Authors

Saidou Balam

Kazutoyo Miura

Imen Ayadi

Drissa Konate

Nathan C Incandela

Valentina Agnolon

Merepen A Guindo

Seidina A S Diakite

Sope Olugbile

Issa Nebie

Sonia M Herrera

Carole Long

Andrey V Kajava

Mahamadou Diakite

Giampietro Corradin

Socrates Herrera

Myriam Arevalo Herrera

Affiliations

Soon will be listed here.

Abstract

Background: 48/45, a gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinant 48/45 protein (r48/45) with sera from -exposed African donors.

Methods: r48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for its cross-reactivity with sera from Burkina Faso, Tanzania, Mali, and Nigeria - In addition, BALB/c mice were immunized with the r48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of NF-54 gametocytes to evaluate the parasite-boosting effect on r48/45 antibody titers. Specific anti-48/45 IgG purified from African sera was used to evaluate the TB activity on using standard mosquito membrane feeding assays (SMFA).

Results: r48/45 protein showed cross-reactivity with sera of individuals from all four African countries, in proportions ranging from 94% (Tanzania) to 40% (Nigeria). Also, the level of cross-reactive antibodies varied significantly between countries (p<0.0001), with a higher antibody level in Mali and the lowest in Nigeria. In addition, antibody levels were higher in adults (≥ 17 years) than young children (≤ 5 years) in both Mali and Tanzania, with a higher proportion of responders in adults (90%) than in children (61%) (p<0.0001) in Mali, where male (75%) and female (80%) displayed similar antibody responses. Furthermore, immunization of mice with gametocytes boosted anti-48/45 antibody responses, recognizing gametocytes in indirect immunofluorescence antibody test. Notably, r48/45 affinity-purified African IgG exhibited a TB activity of 61% against in SMFA.

Conclusion: African sera (exposed only to cross-recognized the r48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of a and cross-protective TB vaccine.

References

. Malaria vaccine: WHO position paper, January 2016 - Recommendations. Vaccine. 2017; 36(25):3576-3577. DOI: 10.1016/j.vaccine.2016.10.047. View

Singh B, Daneshvar C . Human infections and detection of Plasmodium knowlesi. Clin Microbiol Rev. 2013; 26(2):165-84. PMC: 3623376. DOI: 10.1128/CMR.00079-12. View

Datoo M, Dicko A, Tinto H, Ouedraogo J, Hamaluba M, Olotu A . Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial. Lancet. 2024; 403(10426):533-544. DOI: 10.1016/S0140-6736(23)02511-4. View

Arakawa T, Komesu A, Otsuki H, Sattabongkot J, Udomsangpetch R, Matsumoto Y . Nasal immunization with a malaria transmission-blocking vaccine candidate, Pfs25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum. Infect Immun. 2005; 73(11):7375-80. PMC: 1273902. DOI: 10.1128/IAI.73.11.7375-7380.2005. View

Arevalo-Herrera M, Solarte Y, Marin C, Santos M, Castellanos J, Beier J . Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America. Mem Inst Oswaldo Cruz. 2011; 106 Suppl 1:202-11. PMC: 4830685. DOI: 10.1590/s0074-02762011000900025. View

Tachibana M, Suwanabun N, Kaneko O, Iriko H, Otsuki H, Sattabongkot J . Plasmodium vivax gametocyte proteins, Pvs48/45 and Pvs47, induce transmission-reducing antibodies by DNA immunization. Vaccine. 2015; 33(16):1901-8. DOI: 10.1016/j.vaccine.2015.03.008. View

Muthui M, Kamau A, Bousema T, Blagborough A, Bejon P, Kapulu M . Immune Responses to Gametocyte Antigens in a Malaria Endemic Population-The African Context: A Systematic Review and Meta-Analysis. Front Immunol. 2019; 10:2480. PMC: 6817591. DOI: 10.3389/fimmu.2019.02480. View

Zhou Y, Grieser A, Do J, Itsara L, Vaughan A, Ghosh A . Purification and production of Plasmodium falciparum zygotes from in vitro culture using magnetic column and Percoll density gradient. Malar J. 2020; 19(1):192. PMC: 7249376. DOI: 10.1186/s12936-020-03237-1. View

Idris Z, Chan C, Kongere J, Gitaka J, Logedi J, Omar A . High and Heterogeneous Prevalence of Asymptomatic and Sub-microscopic Malaria Infections on Islands in Lake Victoria, Kenya. Sci Rep. 2016; 6:36958. PMC: 5107902. DOI: 10.1038/srep36958. View

10.

Balam S, Olugbile S, Servis C, Diakite M, Dalessandro A, Frank G . Plasmodium falciparum merozoite surface protein 2: epitope mapping and fine specificity of human antibody response against non-polymorphic domains. Malar J. 2014; 13:510. PMC: 4320585. DOI: 10.1186/1475-2875-13-510. View

11.

Merino K, Bansal G, Kumar N . Reduced immunogenicity of Plasmodium falciparum gamete surface antigen (Pfs48/45) in mice after disruption of disulphide bonds - evaluating effect of interferon-γ-inducible lysosomal thiol reductase. Immunology. 2016; 148(4):433-47. PMC: 4948042. DOI: 10.1111/imm.12621. View

12.

Ayadi I, Balam S, Audran R, Bikorimana J, Nebie I, Diakite M . and Orthologous Coiled-Coil Candidates for a Potential Cross-Protective Vaccine. Front Immunol. 2020; 11:574330. PMC: 7609509. DOI: 10.3389/fimmu.2020.574330. View

13.

Arevalo-Herrera M, Vallejo A, Rubiano K, Solarte Y, Marin C, Castellanos A . Recombinant Pvs48/45 antigen expressed in E. coli generates antibodies that block malaria transmission in Anopheles albimanus mosquitoes. PLoS One. 2015; 10(3):e0119335. PMC: 4361554. DOI: 10.1371/journal.pone.0119335. View

14.

Olugbile S, Villard V, Bertholet S, Jafarshad A, Kulangara C, Roussilhon C . Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope. Vaccine. 2011; 29(40):7090-9. PMC: 4165486. DOI: 10.1016/j.vaccine.2011.06.122. View

15.

Griffin J, Hollingsworth T, Reyburn H, Drakeley C, Riley E, Ghani A . Gradual acquisition of immunity to severe malaria with increasing exposure. Proc Biol Sci. 2015; 282(1801):20142657. PMC: 4309004. DOI: 10.1098/rspb.2014.2657. View

16.

Datoo M, Natama M, Some A, Traore O, Rouamba T, Bellamy D . Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet. 2021; 397(10287):1809-1818. PMC: 8121760. DOI: 10.1016/S0140-6736(21)00943-0. View

17.

Feng H, Gupta B, Wang M, Zheng W, Zheng L, Zhu X . Genetic diversity of transmission-blocking vaccine candidate Pvs48/45 in Plasmodium vivax populations in China. Parasit Vectors. 2015; 8:615. PMC: 4665908. DOI: 10.1186/s13071-015-1232-4. View

18.

Messenger L, Shililu J, Irish S, Anshebo G, Tesfaye A, Ye-Ebiyo Y . Insecticide resistance in Anopheles arabiensis from Ethiopia (2012-2016): a nationwide study for insecticide resistance monitoring. Malar J. 2017; 16(1):469. PMC: 5694167. DOI: 10.1186/s12936-017-2115-2. View

19.

Sanchez L, Vidal M, Jairoce C, Aguilar R, Ubillos I, Cuamba I . Antibody responses to the RTS,S/AS01 vaccine and antigens after a booster dose within the phase 3 trial in Mozambique. NPJ Vaccines. 2020; 5:46. PMC: 7272643. DOI: 10.1038/s41541-020-0192-7. View

20.

Chutiyami M, Saravanakumar P, Bello U, Salihu D, Adeleye K, Kolo M . Malaria vaccine efficacy, safety, and community perception in Africa: a scoping review of recent empirical studies. Infection. 2024; 52(5):2007-2028. PMC: 11499420. DOI: 10.1007/s15010-024-02196-y. View