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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Immunol.</journal-id>
<journal-title>Frontiers in Immunology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Immunol.</abbrev-journal-title>
<issn pub-type="epub">1664-3224</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fimmu.2025.1663012</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Immunology</subject>
<subj-group>
<subject>General Commentary</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Commentary: PLGA nanoparticles as an efficient carrier in <italic>Toxoplasma</italic> GAP45: a more effective vaccine against acute toxoplasmosis than traditional ones</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Rattanapitoon</surname>
<given-names>Nathkapach Kaewpitoon</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3123621/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Arunsan</surname>
<given-names>Patpicha</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>La</surname>
<given-names>Nav</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sandoval</surname>
<given-names>Khristine Laguador</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3129219/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rattanapitoon</surname>
<given-names>Schawanya Kaewpitoon</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/3128055/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Parasitic Disease Research, FMC Medical Center of Thailand</institution>, <addr-line>Nakhon Ratchasima</addr-line>,&#xa0;<country>Thailand</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Faculty of Medicine, Vongchavalitkul University</institution>, <addr-line>Nakhon Ratchasima</addr-line>,&#xa0;<country>Thailand</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Faculty of Pediatric and Medicine, International University</institution>, <addr-line>Phnom Penh</addr-line>,&#xa0;<country>Cambodia</country>
</aff>
<aff id="aff4">
<sup>4</sup>
<institution>School of Arts and Sciences, National University</institution>, <addr-line>Pasay City</addr-line>,&#xa0;<country>Philippines</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/65448/overview">Fabrizio Bruschi</ext-link>, University of Pisa, Italy</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/668367/overview">Natassa Pippa</ext-link>, National and Kapodistrian University of Athens, Greece</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Nathkapach Kaewpitoon Rattanapitoon, <email xlink:href="mailto:nathkapach.ratt@gmail.com">nathkapach.ratt@gmail.com</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>27</day>
<month>08</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>16</volume>
<elocation-id>1663012</elocation-id>
<history>
<date date-type="received">
<day>10</day>
<month>07</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>05</day>
<month>08</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2025 Rattanapitoon, Arunsan, La, Sandoval and Rattanapitoon.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Rattanapitoon, Arunsan, La, Sandoval and Rattanapitoon</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<related-article id="RA1" related-article-type="commentary-article" journal-id="Front Immunol" journal-id-type="nlm-ta" xlink:href="10.3389/fimmu.2025.1600399" ext-link-type="doi">A Commentary on <article-title>PLGA nanoparticles as an efficient carrier in <italic>Toxoplasma</italic> GAP45: a more effective vaccine against acute toxoplasmosis than traditional ones</article-title> By Zhou P, Yu Y, Qi W, Wang X, Yu Y, Wang J, Zhang L, Yu Z and Liu T (2025) <italic>Front. Immunol.</italic> 16:1600399. doi:&#xa0;<object-id>10.3389/fimmu.2025.1600399</object-id>
</related-article>
<kwd-group>
<kwd>toxoplasmosis</kwd>
<kwd>subunit vaccine</kwd>
<kwd>PLGA nanoparticles</kwd>
<kwd>TgGAP45</kwd>
<kwd>nanovaccine delivery</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="8"/>
<page-count count="3"/>
<word-count count="699"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Parasite Immunology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<p>The recent study by Zhou et&#xa0;al. (2025) demonstrated the use of PLGA nanoparticles to deliver the TgGAP45 antigen as a subunit vaccine against <italic>Toxoplasma gondii</italic>. This commentary highlights the originality and immunological sophistication of their approach, particularly the elicitation of balanced Th1/Th2/Th17 responses and significant protection in a murine model. We contextualize these findings within the broader vaccine landscape, contrasting them with other nanoparticle and antigen strategies. Furthermore, we propose future research directions not discussed by the authors, including mucosal delivery routes, application in chronic infection models, and systems immunology profiling. These suggestions aim to maximize translational potential and address current gaps in toxoplasmosis vaccine development.</p>
<sec id="s1">
<label>1</label>
<title>Commentary</title>
<p>The study by Zhou et&#xa0;al. (2025) marks a significant advance in the field of vaccine immunology by demonstrating the immunoprotective potential of TgGAP45-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles in acute toxoplasmosis. In contrast to conventional vaccine formulations using Montanide-based emulsions, this work elegantly integrates molecular parasitology, nanotechnology, and immunological profiling to offer a promising strategy for vaccine enhancement.</p>
<p>This study addresses one of the long-standing challenges in toxoplasmosis vaccine development: the need for sustained antigen presentation without compromising safety. The authors convincingly demonstrate that TgGAP45-PLGA nanoparticles not only enhance both humoral and cellular immune responses&#x2014;including mixed Th1/Th2 and IL-17-driven Th17 profiles&#x2014;but also significantly reduce parasite burden in target organs (heart and spleen), surpassing oil-adjuvanted formulations. This is a particularly notable achievement considering previous attempts with subunit vaccines have struggled to achieve robust CD8<sup>+</sup> T-cell activation or durable protection (<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B2">2</xref>).</p>
<p>The mechanistic depth of the study is exemplary. Flow cytometry reveals enhanced dendritic cell maturation (CD83<sup>+</sup>/CD86<sup>+</sup>, MHC-I/II expression), while ELISA and lymphocyte proliferation assays substantiate broad cytokine induction, notably IFN-&#x3b3; and IL-17. These findings align with the necessity for both antigen-specific cytotoxic responses and mucosal immunity in <italic>T. gondii</italic> control (<xref ref-type="bibr" rid="B3">3</xref>).</p>
<p>Compared to earlier efforts using SAG1-based or GRA7-based vaccines (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>), TgGAP45 targets the glideosome&#x2014;a conserved and essential structure for motility and invasion. This strategic antigen selection distinguishes the present study from SAG1-centric vaccines that fail to elicit effective responses against intracellular tachyzoites. Furthermore, PLGA nanoparticles exhibit superior storage stability and safety over liposomes or lipid nanoparticles, which are prone to oxidative degradation (<xref ref-type="bibr" rid="B6">6</xref>).</p>
<p>Despite its many strengths, the study leaves several compelling avenues for future exploration.</p>
<sec id="s1_1">
<label>1.1</label>
<title>Chronic infection model</title>
<p>While this work focuses on acute toxoplasmosis, the bradyzoite stage is responsible for chronic infection and reactivation. Evaluating vaccine efficacy in models using ME49 or VEG strains would enhance translational relevance (<xref ref-type="bibr" rid="B7">7</xref>).</p>
</sec>
<sec id="s1_2">
<label>1.2</label>
<title>Mucosal immunity and oral delivery</title>
<p>Given <italic>T. gondii</italic> is primarily acquired via the gastrointestinal route, oral or intranasal administration of TgGAP45-PLGA could be transformative. PLGA particles are known to be amenable to mucosal delivery and could be formulated with mucoadhesive polymers to promote Peyer&#x2019;s patch uptake (<xref ref-type="bibr" rid="B8">8</xref>).</p>
</sec>
<sec id="s1_3">
<label>1.3</label>
<title>Systems immunology profiling</title>
<p>Bulk or single-cell RNA sequencing of splenocytes or DCs could elucidate transcriptional programs underpinning the observed immune response, enabling biomarker discovery for correlates of protection.</p>
</sec>
<sec id="s1_4">
<label>1.4</label>
<title>Cross-species application</title>
<p>Evaluating this platform in target livestock species (e.g., ovine or porcine models) would address the need for agricultural biosecurity and zoonotic transmission control.</p>
</sec>
<sec id="s1_5">
<label>1.5</label>
<title>Antigen multiplexing</title>
<p>Incorporation of additional antigens&#x2014;e.g., ROP18, GRA14&#x2014;in multivalent PLGA formulations may yield synergistic protective effects and reduce escape mechanisms by parasite stage switching.</p>
</sec>
<sec id="s1_6">
<label>1.6</label>
<title>T-cell epitope mapping</title>
<p>Identification of TgGAP45-derived epitopes presented by MHC-I/MHC-II molecules in vaccinated hosts could inform the rational design of synthetic peptide vaccines and MHC tetramer development for immunomonitoring.</p>
</sec>
</sec>
<sec id="s2" sec-type="conclusion">
<label>2</label>
<title>Conclusion</title>
<p>Zhou et&#xa0;al. have laid a robust foundation for nanotechnology-enabled toxoplasmosis vaccination, and their study stands as a benchmark for rational subunit vaccine engineering. Expanding upon their approach in the directions outlined above could yield a next-generation vaccine that is not only safe and effective but also field-deployable for both human and veterinary applications. Given the zoonotic impact and global prevalence of toxoplasmosis, this line of research is not only scientifically sound but of pressing public health importance.</p>
</sec>
</body>
<back>
<sec id="s3" sec-type="author-contributions">
<title>Author contributions</title>
<p>NR: Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. PA: Writing &#x2013; review &amp; editing. NL: Writing &#x2013; review &amp; editing. KS: Writing &#x2013; review &amp; editing. SR: Supervision, Writing &#x2013; review &amp; editing.</p>
</sec>
<sec id="s4" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare financial support was received for the research and/or publication of this article. This article received publication support from Soon Kaen Phat FMC Co., Ltd. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.</p>
</sec>
<ack>
<title>Acknowledgments</title>
<p>The author would like to thank the <italic>Frontiers in Immunology</italic> editorial team for the opportunity to contribute to the post-publication discourse. No additional contributors were involved in the preparation of this manuscript.</p>
</ack>
<sec id="s5" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s6" sec-type="ai-statement">
<title>Generative AI statement</title>
<p>The author(s) declare that Generative AI was used in the creation of this manuscript. Generative AI (ChatGPT by OpenAI) was used solely to assist in checking the clarity of language, grammar, the appropriateness of structural organization, and references. The ideas, analysis, comparisons, and conclusions presented in the manuscript are entirely original and written by the author.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec id="s7" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors&#xa0;and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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