Evaluation of Four Adjuvant Combinations, IVAX-1, IVAX-2, CpG-1826+Montanide ISA 720 VG and CpG-1018+Montanide ISA 720 VG, for Safety and for Their Ability to Elicit Protective Immune Responses in Mice against a Respiratory Challenge with <i>Chlamydia muridarum</i>

Sukumar Pal; Anatoli Slepenkin; Jiin Felgner; D. Huw Davies; Philip Felgner; Luis M. de la Maza

doi:10.3390/pathogens12070863

Pathogens (Jun 2023)

Evaluation of Four Adjuvant Combinations, IVAX-1, IVAX-2, CpG-1826+Montanide ISA 720 VG and CpG-1018+Montanide ISA 720 VG, for Safety and for Their Ability to Elicit Protective Immune Responses in Mice against a Respiratory Challenge with <i>Chlamydia muridarum</i>

Sukumar Pal,
Anatoli Slepenkin,
Jiin Felgner,
D. Huw Davies,
Philip Felgner,
Luis M. de la Maza

Affiliations

Sukumar Pal: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA
Anatoli Slepenkin: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA
Jiin Felgner: Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
D. Huw Davies: Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
Philip Felgner: Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
Luis M. de la Maza: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA

DOI: https://doi.org/10.3390/pathogens12070863
Journal volume & issue: Vol. 12, no. 7
p. 863

Abstract

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There is an urgent need to produce a vaccine for Chlamydia trachomatis infections. Here, using the Chlamydia muridarum major outer membrane protein (MOMP) as an antigen, four adjuvant combinations IVAX-1 (MPLA+CpG-1018+AddaVax), IVAX-2 (MPLA+CpG-1018+AS03), CpG-1826+Montanide ISA 720 VG (CpG-1826+Mont) and CpG-1018+Montanide ISA 720 VG (CpG-1018+Mont), were tested for their local reactogenicity and ability to elicit protection in BALB/c mice against a respiratory challenge with C. muridarum. Immunization with IVAX-1 or IVAX-2 induced no significant local reactogenicity following intramuscular immunization. In contrast, vaccines containing Montanide resulted in the formation of a local granuloma. Based on the IgG2a/IgG1 ratio in serum, the four adjuvant combinations elicited Th1-biased responses. IVAX-1 induced the highest in vitro neutralization titers while CpG-1018+Mont stimulated the lowest. As determined by the levels of IFN-γ produced by T-cells, the most robust cellular immune responses were elicited in mice immunized with CpG-1018+Mont, while the weakest responses were mounted by mice receiving IVAX-1. Following the respiratory challenge, mice immunized with CpG-1018+Mont lost the least amount of body weight and had the lowest number of C. muridarum inclusion-forming units (IFUs) in the lungs, while those receiving IVAX-2 had lost the most weight and had the highest number of IFUs in their lungs. Animals vaccinated with CpG-1826+Mont had the lightest lungs while those immunized using IVAX-2 had the heaviest. To conclude, due to their safety and adjuvanticity, IVAX formulations should be considered for inclusion in human vaccines against Chlamydia.

Published in Pathogens

ISSN: 2076-0817 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/pathogens

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