The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates.
Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innat...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3355165?pdf=render |
| _version_ | 1818859189137571840 |
|---|---|
| author | Jing Wang Nancy Tricoche Lanying Du Meredith Hunter Bin Zhan Gaddam Goud Elizabeth S Didier Jing Liu Lu Lu Preston A Marx Shibo Jiang Sara Lustigman |
| author_facet | Jing Wang Nancy Tricoche Lanying Du Meredith Hunter Bin Zhan Gaddam Goud Elizabeth S Didier Jing Liu Lu Lu Preston A Marx Shibo Jiang Sara Lustigman |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant. |
| first_indexed | 2024-12-19T09:08:13Z |
| format | Article |
| id | doaj.art-d0fa81bc328a46a89be1a59f6fc6c76d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T09:08:13Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d0fa81bc328a46a89be1a59f6fc6c76d2022-12-21T20:28:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3701910.1371/journal.pone.0037019The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates.Jing WangNancy TricocheLanying DuMeredith HunterBin ZhanGaddam GoudElizabeth S DidierJing LiuLu LuPreston A MarxShibo JiangSara LustigmanAdjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant.http://europepmc.org/articles/PMC3355165?pdf=render |
| spellingShingle | Jing Wang Nancy Tricoche Lanying Du Meredith Hunter Bin Zhan Gaddam Goud Elizabeth S Didier Jing Liu Lu Lu Preston A Marx Shibo Jiang Sara Lustigman The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates. PLoS ONE |
| title | The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates. |
| title_full | The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates. |
| title_fullStr | The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates. |
| title_full_unstemmed | The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates. |
| title_short | The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates. |
| title_sort | adjuvanticity of an o volvulus derived rov asp 1 protein in mice using sequential vaccinations and in non human primates |
| url | http://europepmc.org/articles/PMC3355165?pdf=render |
| work_keys_str_mv | AT jingwang theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT nancytricoche theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT lanyingdu theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT meredithhunter theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT binzhan theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT gaddamgoud theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT elizabethsdidier theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT jingliu theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT lulu theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT prestonamarx theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT shibojiang theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT saralustigman theadjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT jingwang adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT nancytricoche adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT lanyingdu adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT meredithhunter adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT binzhan adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT gaddamgoud adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT elizabethsdidier adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT jingliu adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT lulu adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT prestonamarx adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT shibojiang adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates AT saralustigman adjuvanticityofanovolvulusderivedrovasp1proteininmiceusingsequentialvaccinationsandinnonhumanprimates |