Protection against a chlamydial respiratory challenge by a chimeric vaccine formulated with the Chlamydia muridarum major outer membrane protein variable domains using the Neisseria lactamica porin B as a scaffold

Delia F Tifrea; Sukumar Pal; Jeff Fairman; Paola Massari; Luis M de la Maza

doi:10.1038/s41541-020-0182-9

Protection against a chlamydial respiratory challenge by a chimeric vaccine formulated with the Chlamydia muridarum major outer membrane protein variable domains using the Neisseria lactamica porin B as a scaffold

NPJ Vaccines. 2020 May 8;5(1):37. doi: 10.1038/s41541-020-0182-9. eCollection 2020.

Authors

Delia F Tifrea¹, Sukumar Pal¹, Jeff Fairman², Paola Massari³, Luis M de la Maza¹

Affiliations

¹ 1Department of Pathology and Laboratory Medicine, University of California, Irvine, Medical Sciences I, Room D440, Irvine, California 92697-4800 USA.
² Sutrovax, Inc., 400 E Jamie Court, Suite 205, South San Francisco, California 94080 USA.
³ 3Department of Immunology, Tufts University School of Medicine, Jaharis, 512C 150 Harrison Avenue, Boston, Massachusetts 02111 USA.

Abstract

Chlamydia trachomatis is the most frequently detected sexually transmitted bacterial pathogen in the world. Attempts to control these infections with screening programs and antibiotics have failed and, therefore, a vaccine is the best approach to control this epidemic. The Chlamydia major outer membrane protein (MOMP) is the most protective subunit vaccine so far tested. Protection induced by MOMP is, in part, dependent on its tertiary structure. We have previously described new recombinant antigens composed of the Neisseria lactamica PorB engineered to express the variable domains (VD) from Chlamydia muridarum MOMP. Here we tested antigens containing each individual MOMP VD and different VD combinations. Following immunization, mice were challenged intranasally with C. muridarum. Our results show that three constructs, PorB/VD1-3, PorB/VD1-4, and PorB/VD1-2-4, elicited high serum IgG titers in vivo, significant IFN-γ levels upon T cells re-stimulation in vitro, and evidence of protective immunity in vivo. PorB/VD1-3, PorB/VD1-4, and PorB/VD1-2-4 immunized mice lost less body weight, had lighter lungs, and decreased numbers of inclusion forming units (IFUs) in lungs than other PorB/VD construct tested and mock PBS-immunized mice. These results suggest that this approach may be a promising alternative to the use of MOMP in a Chlamydia vaccine.

Keywords: Protein vaccines.