Bioactive Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles (BEACONs) for Mucosal Vaccination Against Genital Herpes

Bhagchandani, S. H.; Ehrenzeller, S.; Pires, I. S.; Chaudhary, N.; Booth, C. J.; Guedes de Sa, K. S.; Kwon, D.-i.; Li, S.; Olszowka, A.; Hudak, A.; Fischer, S.; Bayarri-Olmos, R.; Iwasaki, A.

doi:10.1101/2025.07.31.667899

bioRxiv · 10.1101/2025.07.31.667899

Bioactive Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles (BEACONs) for Mucosal Vaccination Against Genital Herpes

Bhagchandani, S. H.·Ehrenzeller, S.·Pires, I. S.·Chaudhary, N.·Booth, C. J.·Guedes de Sa, K. S.·Kwon, D.-i.·Li, S.·Olszowka, A.·Hudak, A.·Fischer, S.·Bayarri-Olmos, R.·Iwasaki, A.

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Abstract

Genital herpes, caused by herpes simplex virus-2 (HSV-2), remains a prevalent sexually transmitted infection with no available vaccine. Effective local immunity--including tissue-resident memory T cells (TRMs) and luminal antibodies--provides immediate viral control. Here, we developed Bioactive Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles (BEACON) formed via electrostatic interactions between CpG oligodeoxynucleotides (CpG ODN) and the chemokine CXCL9. This adjuvant enhances antigen-presenting cell engagement and innate immune signaling, promotes CD8+ T cell recruitment, and reduces local neutrophilic inflammation relative to CpG ODN. Co-administered vaginally with HSV-2 glycoproteins following intramuscular priming, BEACON improved protection against HSV-2 by increasing local CD8+ TRM populations and mucosal IgG and IgA responses. Vaccine-mediated protection required local delivery of both antigen and adjuvant, and was significantly reduced by CD8+ T cell or B cell depletion. These findings highlight the potential of engineered mucosal adjuvants for vaccines targeting genital herpes and other sexually transmitted infections. One-sentence summaryWe developed BEACON, a mucosal adjuvant that elicits protective immunity against genital herpes simplex virus 2 infection in mice.

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Bhagchandani, S. H., Ehrenzeller, S., Pires, I. S., Chaudhary, N., Booth, C. J., Guedes de Sa, K. S., Kwon, D.-i., Li, S., Olszowka, A., Hudak, A., Fischer, S., Bayarri-Olmos, R., Iwasaki, A.. 2025-08-02. Bioactive Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles (BEACONs) for Mucosal Vaccination Against Genital Herpes. https://doi.org/10.1101/2025.07.31.667899

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