Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jul 7;10(7):e0004797.
doi: 10.1371/journal.pntd.0004797. eCollection 2016 Jul.

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice

Jessica A Hess  1 , Bin Zhan  2   3 , April R Torigian  1 , John B Patton  1 , Nikolai Petrovsky  4   5 , Tingting Zhan  6 , Maria Elena Bottazzi  2   3 , Peter J Hotez  2   3 , Thomas R Klei  7 , Sara Lustigman  8 , David Abraham  1
Affiliations

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice

Jessica A Hess et al. PLoS Negl Trop Dis. .

Abstract

Background: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses.

Methodology/ principal findings: Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2.

Conclusions/significance: The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.

PubMed Disclaimer

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: NP is associated with Vaxine Pty Ltd, which has commercial interests in Advax adjuvants. Novartis Vaccines & Diagnostics provided MF59 via a Material Transfer Agreement with the authors and authorized publication of the findings in exchange for access to the data.

Figures

Fig 1
Fig 1. Survival of Onchocerca volvulus in mice immunized with Ov-103 or Ov-RAL-2 without adjuvant.
Effect of immunization with Ov-103 or Ov-RAL-2 without adjuvant on the development of protective immunity to Onchocerca volvulus larvae in mice. Each dot represents percent larval recovery from an individual animal. Data presented are mean ± standard error.
Fig 2
Fig 2. Survival of Onchocerca volvulus in mice immunized with Ov-103 with five different adjuvants.
Effect of immunization with Ov-103 formulated with the adjuvants alum, Advax 1, Advax 2, CpG or MF59 on the development of protective immunity to Onchocerca volvulus larvae in mice. Each dot represents percent larval recovery from an individual animal. Data lines presented are mean ± standard error. Asterisk represents statistical difference in larval recoveries, p value ≤ 0.05. Dotted line is placed at the 95th confidence interval for parasite recovery from control animals. % Reduction = percent reduction in parasite survival in immunized mice as compared to controls. Host Protection = percentage of mice in the immunized group with parasite recovery levels below the 95thconfidence interval for parasite recovery from control animals.
Fig 3
Fig 3. Survival of Onchocerca volvulus in mice immunized with Ov-RAL-2 with three different adjuvants.
Effect of immunization with Ov-RAL-2 formulated with the adjuvants alum, Advax 2 or MF59 on the development of protective immunity to Onchocerca volvulus larvae in mice. Each dot represents percent larval recovery from an individual animal. Data lines presented are mean ± standard error. Asterisk represents statistical difference in larval recoveries, p value ≤ 0.05. Dotted line is placed at the 95th confidence interval for parasite recovery from control animals. % Reduction = percent reduction in parasite survival in immunized mice as compared to controls. Host Protection = percentage of mice in the immunized group with parasite recovery levels below the 95thconfidence interval for parasite recovery from control animals.
Fig 4
Fig 4. Survival of Onchocerca volvulus in mice immunized with Ov-103 and Ov-RAL-2 co-administered with three different adjuvants.
Effect of immunization with the Ov-103 and Ov-RAL-2 co-administered vaccines formulated with the adjuvants alum, Advax 2 or MF59 on the development of protective immunity to Onchocerca volvulus larvae in mice. Each dot represents percent larval recovery from an individual animal. Data lines presented are mean ± standard error. Asterisk represents statistical difference in larval recoveries, p value ≤ 0.05. Dotted line is placed at the 95th confidence interval for parasite recovery from control animals. % Reduction = percent reduction in parasite survival in immunized mice as compared to controls. Host Protection = percentage of mice in the immunized group with parasite recovery levels below the 95thconfidence interval for parasite recovery from control animals.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Forouzanfar MH, Alexander L, Anderson HR, Bachman VF, Biryukov S, Brauer M, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(10010):2287–323. Epub 2015/09/15. 10.1016/S0140-6736(15)00128-2 - DOI - PMC - PubMed
    1. Foltz JL, Makumbi I, Sejvar JJ, Malimbo M, Ndyomugyenyi R, Atai-Omoruto AD, et al. An Epidemiologic Investigation of Potential Risk Factors for Nodding Syndrome in Kitgum District, Uganda. PloS one. 2013;8(6):e66419 Epub 2013/07/05. 10.1371/journal.pone.0066419 - DOI - PMC - PubMed
    1. Wamala JF, Malimbo M, Tepage F, Lukwago L, Okot CL, Cannon RO, et al. Nodding Syndrome May Be Only the Ears of the Hippo. PLoS neglected tropical diseases. 2015;9(8):e0003880 Epub 2015/08/14. 10.1371/journal.pntd.0003880 - DOI - PMC - PubMed
    1. Diawara L, Traore MO, Badji A, Bissan Y, Doumbia K, Goita SF, et al. Feasibility of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: first evidence from studies in Mali and Senegal. PLoS neglected tropical diseases. 2009;3(7):e497 Epub 2009/07/22. 10.1371/journal.pntd.0000497 - DOI - PMC - PubMed
    1. Boatin BA, Richards FO Jr. Control of onchocerciasis. Advances in parasitology. 2006;61:349–94. Epub 2006/06/01. 10.1016/S0065-308X(05)61009-3 . - DOI - PubMed

Publication types

MeSH terms