MtsB, a hydrophobic membrane protein of Streptococcus iniae, is an effective subunit vaccine candidate

Within a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people worldwide with a death toll over 2 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The tightly closed conformation is stabilized by fatty acid and polysorbate 80 binding at the receptor binding domains (RBDs) and the N terminal domains (NTDs) respectively. Additionally, we identified an important pH switch in the WT S-Trimer that shows dramatic conformational change and accounts for its increased stability at lower pH. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine. IMPORTANCE Effective vaccine against SARS-CoV-2 is critical to end the COVID-19 pandemic. Here, using Trimer-Tag technology, we are able to produce stable and large quantities of WT S-Trimer, a subunit vaccine candidate for COVID-19 with high safety and efficacy from animal and Phase 1 clinical trial studies. Cryo-EM structures of the S-Trimer subunit vaccine candidate show that it predominately adopts tightly closed pre-fusion state, and resembles that of the native and full-length spike in detergent, confirming its structural integrity. WT S-Trimer is currently being evaluated in global Phase 2/3 clinical trial. Combining with published structures of the S protein, we also propose a model to dissect the conformation change of the spike protein before receptor binding.

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Kinetoplastid Membrane Protein-11 as a Vaccine Candidate and a Virulence Factor in Leishmania

Frontiers in Immunology ◽

10.3389/fimmu.2015.00524 ◽

2015 ◽

Vol 6 ◽

Cited By ~ 11

Author(s):

Sergio Coutinho Furtado de Mendonça ◽

Léa Cysne-Finkelstein ◽

Denise Cristina de Souza Matos

Keyword(s):

Membrane Protein ◽

Virulence Factor ◽

Vaccine Candidate

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A shared antigen among Vibrio species: Outer membrane protein-OmpK as a versatile Vibriosis vaccine candidate in Orange-spotted grouper (Epinephelus coioides)

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2010.02.010 ◽

2010 ◽

Vol 28 (5-6) ◽

pp. 952-956 ◽

Cited By ~ 40

Author(s):

Ningqiu Li ◽

Zhihui Yang ◽

Junjie Bai ◽

Xiaozhe Fu ◽

Lihui Liu ◽

...

Keyword(s):

Membrane Protein ◽

Outer Membrane ◽

Outer Membrane Protein ◽

Vaccine Candidate ◽

Vibrio Species ◽

Epinephelus Coioides

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A Recombinant Chlamydia trachomatis MOMP Vaccine Elicits Cross-serogroup Protection in Mice Against Vaginal Shedding and Infertility

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz438 ◽

2019 ◽

Vol 221 (2) ◽

pp. 191-200 ◽

Cited By ~ 2

Author(s):

Delia F Tifrea ◽

Sukumar Pal ◽

Luis M de la Maza

Keyword(s):

Chlamydia Trachomatis ◽

Membrane Protein ◽

Immune Responses ◽

Outer Membrane ◽

Outer Membrane Protein ◽

Subunit Vaccine ◽

Bacterial Pathogen ◽

Male Mice ◽

Fertility Rates ◽

Sexually Transmitted

Abstract Background Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a C. trachomatis recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection. Methods Female C3H/HeN mice were vaccinated by mucosal and systemic routes with C. trachomatis serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with serovars D (UW-3/Cx), D (UCI-96/Cx), E (IOL-43), or F (N.I.1). CpG-1826 and Montanide ISA 720 were used as adjuvants. Results Immune responses following vaccination were more robust against the most closely related serovars. Following a genital challenge (as determined by number of mice with positive vaginal cultures, number of positive cultures, number of inclusion forming units recovered, and number of days with positive cultures) mice challenged with C. trachomatis serovars of the same complex were protected but not those challenged with serovar F (N.I.1) from a different subcomplex. Females were caged with male mice. Based on fertility rates, number of embryos, and hydrosalpinx formation, vaccinated mice were protected against challenges with serovars D (UW-3/Cx), D (UCI-96/Cx), and E (IOL-43) but not F (N.I.1). Conclusions This is the first subunit vaccine shown to protect mice against infection, pathology, and infertility caused by different C. trachomatis serovars.

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