Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies
| Autor: | Scott Jones, Tania Rivera-Hernandez, Nikolai Petrovsky, Livia Brunner, Amanda J. Cork, Johanna Richter, Nicolas Collin, David Goldblatt, Mira Syahira Rhyme, Maria Lawrenz, Mark J. Walker, Celia Segui-Perez |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_treatment Aluminum Hydroxide Microbiology Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine Immune system Adjuvants Immunologic Antigen Streptococcal Infections Virology medicine Animals 030212 general & internal medicine 030304 developmental biology Immunity Cellular 0303 health sciences Streptococcus vaccine business.industry group A Streptococcus Streptococcal Vaccines Antibody titer Streptococcus infection Therapeutics and Prevention vaccines Opsonin Proteins Th1 Cells Antibodies Bacterial QS21 QR1-502 Immunization adjuvants Immunoglobulin G invasive disease Immunology Cytokines Female business Adjuvant Research Article |
| Zdroj: | mBio mBio, Vol 11, Iss 2, p e00122-20 (2020) mBio, Vol 11, Iss 2 (2020) |
| ISSN: | 2150-7511 2161-2129 |
| Popis: | Availability of a group A Streptococcus vaccine remains an unmet public health need. Here, we tested different adjuvant formulations to improve the protective efficacy of non-M protein vaccine Combo5 in an invasive disease model. We show that novel adjuvants can dramatically shape the type of immune response developed following immunization with Combo5 and significantly improve protection. In addition, protection afforded by Combo5 is not mediated by opsonizing antibodies, believed to be the main correlate of protection against GAS infections. Overall, this report highlights the importance of adjuvant selection in raising protective immune responses against GAS invasive infection. Adjuvants that can provide a more balanced Th1/Th2-type response may be required to optimize protection of GAS vaccines, particularly those based on non-M protein antigens. Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. However, Combo5 with the addition of aluminum hydroxide (alum) as an adjuvant failed to protect against invasive GAS infection of mice. Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. SMQ, but not alum, generated strong interleukin-6 (IL-6), gamma interferon (IFN-γ), and tumor necrosis alpha (TNF-α) responses. This work highlights the importance of adjuvant selection for non-M protein-based GAS vaccines to optimize immune responses and protective efficacy. |
| Databáze: | OpenAIRE |
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