Selection of combination adjuvants for enhanced immunogenicity of a recombinant CelTOS vaccine against Plasmodium falciparum

Recently, there has been significant interest in developing combination adjuvants to achieve efficient vaccines. However, it remains uncertain which combinations of adjuvants could best enhance the immune response to the recombinant antigen. In the current study, to improve the immunogenicity of Pla...

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Veröffentlicht in:Biochemical and biophysical research communications 2025-02, Vol.748, p.151310, Article 151310
Hauptverfasser: Pirahmadi, Sakineh, Zargar, Mostafa, Pourhashem, Zeinab, Vand-Rajabpour, Hediyeh, Sani, Jafar J., Yousefi, Hemn, Afzali, Shima, Zakeri, Sedigheh, Mehrizi, Akram Abouie
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creator Pirahmadi, Sakineh
Zargar, Mostafa
Pourhashem, Zeinab
Vand-Rajabpour, Hediyeh
Sani, Jafar J.
Yousefi, Hemn
Afzali, Shima
Zakeri, Sedigheh
Mehrizi, Akram Abouie
description Recently, there has been significant interest in developing combination adjuvants to achieve efficient vaccines. However, it remains uncertain which combinations of adjuvants could best enhance the immune response to the recombinant antigen. In the current study, to improve the immunogenicity of Plasmodium falciparum cell traversal protein for ookinetes and sporozoites (PfCelTOS), we tested three different adjuvants: MPL, Poly I:C, and QS-21 alone or in a triple mixture (MPL/Poly I:C/QS-21; MPQ) and a dual mixture (Poly I:C/QS-21; PQ). BALB/c mice were immunized with recombinant PfCelTOS, either alone or combined with MPL, Poly I:C, QS-21, or with dual and triple adjuvant mixtures. Humoral and cellular immune responses were assessed in the various mouse groups, along with the functional activity of anti-PfCelTOS antibodies in oocyst inhibition. The results showed that administering the PfCelTOS antigen with triple or dual adjuvant mixtures significantly increased specific antibody levels, as well as IFN-ɣ and TNF cytokine production (P  0.05). The findings indicate that the dual mixture of Poly I:C and QS-21 is the most effective formulation for a vaccine against PfCelTOS. This discovery has important cost and safety implications by minimizing the adjuvants required to achieve an optimal immune response. •Combination adjuvants enhance the immunogenicity of recombinant malaria vaccine.•Specific combination adjuvants should be evaluated with recombinant antigen.•Two different adjuvant mixtures (MPQ & PQ) were tested in combination with PfCelTOS.•Both adjuvant mixtures increased transmission-reducing activity in SMFA assay.•Dual adjuvant mixture (PQ) is an effective adjuvant for vaccine against PfCelTOS.
doi_str_mv 10.1016/j.bbrc.2025.151310
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However, it remains uncertain which combinations of adjuvants could best enhance the immune response to the recombinant antigen. In the current study, to improve the immunogenicity of Plasmodium falciparum cell traversal protein for ookinetes and sporozoites (PfCelTOS), we tested three different adjuvants: MPL, Poly I:C, and QS-21 alone or in a triple mixture (MPL/Poly I:C/QS-21; MPQ) and a dual mixture (Poly I:C/QS-21; PQ). BALB/c mice were immunized with recombinant PfCelTOS, either alone or combined with MPL, Poly I:C, QS-21, or with dual and triple adjuvant mixtures. Humoral and cellular immune responses were assessed in the various mouse groups, along with the functional activity of anti-PfCelTOS antibodies in oocyst inhibition. The results showed that administering the PfCelTOS antigen with triple or dual adjuvant mixtures significantly increased specific antibody levels, as well as IFN-ɣ and TNF cytokine production (P &lt; 0.05), compared to PfCelTOS alone or combined with single adjuvants. These vaccine adjuvant mixtures also enhanced transmission-reducing activity (TRA), resulting in 76%–84% reductions in oocyst intensity in functional assays. Interestingly, comparable antibody levels and functional inhibitory activity were observed in the groups that received antigen with both dual and triple adjuvants (P &gt; 0.05). The findings indicate that the dual mixture of Poly I:C and QS-21 is the most effective formulation for a vaccine against PfCelTOS. This discovery has important cost and safety implications by minimizing the adjuvants required to achieve an optimal immune response. •Combination adjuvants enhance the immunogenicity of recombinant malaria vaccine.•Specific combination adjuvants should be evaluated with recombinant antigen.•Two different adjuvant mixtures (MPQ &amp; PQ) were tested in combination with PfCelTOS.•Both adjuvant mixtures increased transmission-reducing activity in SMFA assay.•Dual adjuvant mixture (PQ) is an effective adjuvant for vaccine against PfCelTOS.</description><identifier>ISSN: 0006-291X</identifier><identifier>ISSN: 1090-2104</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2025.151310</identifier><identifier>PMID: 39809136</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject><![CDATA[Adjuvants, Immunologic - administration & dosage ; Adjuvants, Immunologic - pharmacology ; Adjuvants, Vaccine - pharmacology ; Animals ; Antibodies, Protozoan - immunology ; Combination adjuvant ; Female ; Immunogenicity, Vaccine ; Lipid A - administration & dosage ; Lipid A - analogs & derivatives ; Lipid A - immunology ; Lipid A - pharmacology ; Malaria vaccine ; Malaria Vaccines - administration & dosage ; Malaria Vaccines - immunology ; Malaria, Falciparum - immunology ; Malaria, Falciparum - prevention & control ; Mice ; Mice, Inbred BALB C ; PfCelTOS ; Plasmodium falciparum - immunology ; Poly I-C - administration & dosage ; Poly I-C - immunology ; Poly I-C - pharmacology ; Protozoan Proteins - immunology ; Saponins - immunology ; Saponins - pharmacology ; TLR agonist ; Transmission blocking vaccine ; Vaccines, Synthetic - administration & dosage ; Vaccines, Synthetic - immunology]]></subject><ispartof>Biochemical and biophysical research communications, 2025-02, Vol.748, p.151310, Article 151310</ispartof><rights>2025 Elsevier Inc.</rights><rights>Copyright © 2025 Elsevier Inc. 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Zargar, Mostafa ; Pourhashem, Zeinab ; Vand-Rajabpour, Hediyeh ; Sani, Jafar J. ; Yousefi, Hemn ; Afzali, Shima ; Zakeri, Sedigheh ; Mehrizi, Akram Abouie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1526-ca6349fe84ca2c48935f12a481cd9b6ba805cb0d709b4313d01daef6cdc2e4c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Adjuvants, Immunologic - administration &amp; dosage</topic><topic>Adjuvants, Immunologic - pharmacology</topic><topic>Adjuvants, Vaccine - pharmacology</topic><topic>Animals</topic><topic>Antibodies, Protozoan - immunology</topic><topic>Combination adjuvant</topic><topic>Female</topic><topic>Immunogenicity, Vaccine</topic><topic>Lipid A - administration &amp; dosage</topic><topic>Lipid A - analogs &amp; derivatives</topic><topic>Lipid A - immunology</topic><topic>Lipid A - pharmacology</topic><topic>Malaria vaccine</topic><topic>Malaria Vaccines - administration &amp; dosage</topic><topic>Malaria Vaccines - immunology</topic><topic>Malaria, Falciparum - immunology</topic><topic>Malaria, Falciparum - prevention &amp; control</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>PfCelTOS</topic><topic>Plasmodium falciparum - immunology</topic><topic>Poly I-C - administration &amp; dosage</topic><topic>Poly I-C - immunology</topic><topic>Poly I-C - pharmacology</topic><topic>Protozoan Proteins - immunology</topic><topic>Saponins - immunology</topic><topic>Saponins - pharmacology</topic><topic>TLR agonist</topic><topic>Transmission blocking vaccine</topic><topic>Vaccines, Synthetic - administration &amp; dosage</topic><topic>Vaccines, Synthetic - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pirahmadi, Sakineh</creatorcontrib><creatorcontrib>Zargar, Mostafa</creatorcontrib><creatorcontrib>Pourhashem, Zeinab</creatorcontrib><creatorcontrib>Vand-Rajabpour, Hediyeh</creatorcontrib><creatorcontrib>Sani, Jafar J.</creatorcontrib><creatorcontrib>Yousefi, Hemn</creatorcontrib><creatorcontrib>Afzali, Shima</creatorcontrib><creatorcontrib>Zakeri, Sedigheh</creatorcontrib><creatorcontrib>Mehrizi, Akram Abouie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pirahmadi, Sakineh</au><au>Zargar, Mostafa</au><au>Pourhashem, Zeinab</au><au>Vand-Rajabpour, Hediyeh</au><au>Sani, Jafar J.</au><au>Yousefi, Hemn</au><au>Afzali, Shima</au><au>Zakeri, Sedigheh</au><au>Mehrizi, Akram Abouie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selection of combination adjuvants for enhanced immunogenicity of a recombinant CelTOS vaccine against Plasmodium falciparum</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2025-02-08</date><risdate>2025</risdate><volume>748</volume><spage>151310</spage><pages>151310-</pages><artnum>151310</artnum><issn>0006-291X</issn><issn>1090-2104</issn><eissn>1090-2104</eissn><abstract>Recently, there has been significant interest in developing combination adjuvants to achieve efficient vaccines. However, it remains uncertain which combinations of adjuvants could best enhance the immune response to the recombinant antigen. In the current study, to improve the immunogenicity of Plasmodium falciparum cell traversal protein for ookinetes and sporozoites (PfCelTOS), we tested three different adjuvants: MPL, Poly I:C, and QS-21 alone or in a triple mixture (MPL/Poly I:C/QS-21; MPQ) and a dual mixture (Poly I:C/QS-21; PQ). BALB/c mice were immunized with recombinant PfCelTOS, either alone or combined with MPL, Poly I:C, QS-21, or with dual and triple adjuvant mixtures. Humoral and cellular immune responses were assessed in the various mouse groups, along with the functional activity of anti-PfCelTOS antibodies in oocyst inhibition. The results showed that administering the PfCelTOS antigen with triple or dual adjuvant mixtures significantly increased specific antibody levels, as well as IFN-ɣ and TNF cytokine production (P &lt; 0.05), compared to PfCelTOS alone or combined with single adjuvants. These vaccine adjuvant mixtures also enhanced transmission-reducing activity (TRA), resulting in 76%–84% reductions in oocyst intensity in functional assays. Interestingly, comparable antibody levels and functional inhibitory activity were observed in the groups that received antigen with both dual and triple adjuvants (P &gt; 0.05). The findings indicate that the dual mixture of Poly I:C and QS-21 is the most effective formulation for a vaccine against PfCelTOS. This discovery has important cost and safety implications by minimizing the adjuvants required to achieve an optimal immune response. •Combination adjuvants enhance the immunogenicity of recombinant malaria vaccine.•Specific combination adjuvants should be evaluated with recombinant antigen.•Two different adjuvant mixtures (MPQ &amp; PQ) were tested in combination with PfCelTOS.•Both adjuvant mixtures increased transmission-reducing activity in SMFA assay.•Dual adjuvant mixture (PQ) is an effective adjuvant for vaccine against PfCelTOS.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39809136</pmid><doi>10.1016/j.bbrc.2025.151310</doi><orcidid>https://orcid.org/0000-0001-9502-0407</orcidid></addata></record>
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subjects Adjuvants, Immunologic - administration & dosage
Adjuvants, Immunologic - pharmacology
Adjuvants, Vaccine - pharmacology
Animals
Antibodies, Protozoan - immunology
Combination adjuvant
Female
Immunogenicity, Vaccine
Lipid A - administration & dosage
Lipid A - analogs & derivatives
Lipid A - immunology
Lipid A - pharmacology
Malaria vaccine
Malaria Vaccines - administration & dosage
Malaria Vaccines - immunology
Malaria, Falciparum - immunology
Malaria, Falciparum - prevention & control
Mice
Mice, Inbred BALB C
PfCelTOS
Plasmodium falciparum - immunology
Poly I-C - administration & dosage
Poly I-C - immunology
Poly I-C - pharmacology
Protozoan Proteins - immunology
Saponins - immunology
Saponins - pharmacology
TLR agonist
Transmission blocking vaccine
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - immunology
title Selection of combination adjuvants for enhanced immunogenicity of a recombinant CelTOS vaccine against Plasmodium falciparum
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