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Volume 14
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10.3390/vaccines14020192
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Article

Carrier-Protein-Free Pneumococcal Glycoconjugate Vaccines Enabled by SPAAC: Serotype 15C CPS–PADRE Conjugates and the Impact of an RR Cleavage Motif

by
Huimin Yang
1,†,
Zeyu Liao
1,†,
Yingjie Zhong
1,
Qi Gao
2,
Hangqi Zhang
1,* and
Chengli Zong
1,*
1
School of Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou 570228, China
2
Maxvax Biotechnology Co., Ltd., Chengdu 610200, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Vaccines 2026, 14(2), 192; https://doi.org/10.3390/vaccines14020192
Submission received: 24 December 2025 / Revised: 12 February 2026 / Accepted: 16 February 2026 / Published: 19 February 2026
(This article belongs to the Special Issue Protective Immunity and Adjuvant Vaccines)
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Abstract

Background/Objectives: Polysaccharide-protein conjugate vaccines have proven highly effective, yet they remain limited by manufacturing complexity, cost, and variable performance across serotypes, while carrier proteins can add unwanted immunological and production burdens. To address these constraints, we explored a carrier-protein-free conjugate vaccine concept in which a broadly MHC class II-binding helper epitope (PADRE) replaces the conventional protein carrier to provide T-cell help for a pneumococcal capsular polysaccharide antigen. Methods: Using serotype 15C CPS as a model, we generated CPS–PADRE conjugates and compared designs with or without a putative cleavable motif (RR) at the junction, alongside a conventional protein conjugate as a benchmark. Results: In mice, the CPS–protein conjugate induced the strongest CPS-specific IgG response, whereas CPS–PADRE conjugates elicited clear but overall lower antibody levels. Notably, incorporation of the cleavable motif did not improve immunogenicity and instead reduced humoral responses relative to the non-cleavable design. Conclusion: These findings support the feasibility of carrier-protein-free polysaccharide-peptide conjugate vaccines, while highlighting that cleavable junctions are not universally advantageous and must be empirically optimized for polysaccharide-helper epitope architectures.
Keywords: Streptococcus pneumoniae; serotype 15C; capsular polysaccharide; PADRE; SPAAC; CDAP; DOSY NMR; glycoconjugate vaccine Streptococcus pneumoniae; serotype 15C; capsular polysaccharide; PADRE; SPAAC; CDAP; DOSY NMR; glycoconjugate vaccine

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MDPI and ACS Style

Yang, H.; Liao, Z.; Zhong, Y.; Gao, Q.; Zhang, H.; Zong, C. Carrier-Protein-Free Pneumococcal Glycoconjugate Vaccines Enabled by SPAAC: Serotype 15C CPS–PADRE Conjugates and the Impact of an RR Cleavage Motif. Vaccines 2026, 14, 192. https://doi.org/10.3390/vaccines14020192

AMA Style

Yang H, Liao Z, Zhong Y, Gao Q, Zhang H, Zong C. Carrier-Protein-Free Pneumococcal Glycoconjugate Vaccines Enabled by SPAAC: Serotype 15C CPS–PADRE Conjugates and the Impact of an RR Cleavage Motif. Vaccines. 2026; 14(2):192. https://doi.org/10.3390/vaccines14020192

Chicago/Turabian Style

Yang, Huimin, Zeyu Liao, Yingjie Zhong, Qi Gao, Hangqi Zhang, and Chengli Zong. 2026. "Carrier-Protein-Free Pneumococcal Glycoconjugate Vaccines Enabled by SPAAC: Serotype 15C CPS–PADRE Conjugates and the Impact of an RR Cleavage Motif" Vaccines 14, no. 2: 192. https://doi.org/10.3390/vaccines14020192

APA Style

Yang, H., Liao, Z., Zhong, Y., Gao, Q., Zhang, H., & Zong, C. (2026). Carrier-Protein-Free Pneumococcal Glycoconjugate Vaccines Enabled by SPAAC: Serotype 15C CPS–PADRE Conjugates and the Impact of an RR Cleavage Motif. Vaccines, 14(2), 192. https://doi.org/10.3390/vaccines14020192

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