. 2019 Mar 2;11(3):212.

doi: 10.3390/v11030212.

Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

Danielle R Adney¹, Lingshu Wang², Neeltje van Doremalen³, Wei Shi⁴, Yi Zhang⁵, Wing-Pui Kong⁶, Megan R Miller⁷, Trenton Bushmaker⁸, Dana Scott⁹, Emmie de Wit¹⁰, Kayvon Modjarrad¹¹, Nikolai Petrovsky¹², Barney S Graham¹³, Richard A Bowen¹⁴, Vincent J Munster^{15

16}

Affiliations

¹ Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80521, USA. Danielle.Adney@colostate.edu.
² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. wangling@niaid.nih.gov.
³ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. neeltje.vandoremalen@nih.gov.
⁴ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. shiw@mail.nih.gov.
⁵ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. yi.zhang3@nih.gov.
⁶ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. wkong@mail.nih.gov.
⁷ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. megan.r.miller@colostate.edu.
⁸ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. bushmakertj@niaid.nih.gov.
⁹ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. dana.scott@nih.gov.
¹⁰ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. Emmie.deWit@nih.gov.
¹¹ Military HIV Research, Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. kmodjarrad@hivresearch.org.
¹² Flinders University and Vaxine Pty Ltd, Flinders Medical Centre, Bedford Park, SA 5042, Australia. nikolai.petrovsky@flinders.edu.au.
¹³ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. bgraham@mail.nih.gov.
¹⁴ Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80521, USA. rbowen@rams.colostate.edu.
¹⁵ Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80521, USA. Vincent.munster@nih.gov.
¹⁶ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. Vincent.munster@nih.gov.

PMID: 30832356
PMCID: PMC6466352
DOI: 10.3390/v11030212

Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

Danielle R Adney et al. Viruses. 2019.

. 2019 Mar 2;11(3):212.

doi: 10.3390/v11030212.

Authors

Affiliations

¹ Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80521, USA. Danielle.Adney@colostate.edu.
² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. wangling@niaid.nih.gov.
³ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. neeltje.vandoremalen@nih.gov.
⁴ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. shiw@mail.nih.gov.
⁵ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. yi.zhang3@nih.gov.
⁶ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. wkong@mail.nih.gov.
⁷ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. megan.r.miller@colostate.edu.
⁸ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. bushmakertj@niaid.nih.gov.
⁹ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. dana.scott@nih.gov.
¹⁰ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. Emmie.deWit@nih.gov.
¹¹ Military HIV Research, Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. kmodjarrad@hivresearch.org.
¹² Flinders University and Vaxine Pty Ltd, Flinders Medical Centre, Bedford Park, SA 5042, Australia. nikolai.petrovsky@flinders.edu.au.
¹³ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA. bgraham@mail.nih.gov.
¹⁴ Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80521, USA. rbowen@rams.colostate.edu.
¹⁵ Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80521, USA. Vincent.munster@nih.gov.
¹⁶ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. Vincent.munster@nih.gov.

PMID: 30832356
PMCID: PMC6466352
DOI: 10.3390/v11030212

Abstract

MERS-CoV is present in dromedary camels throughout the Middle East and Africa. Dromedary camels are the primary zoonotic reservoir for human infections. Interruption of the zoonotic transmission chain from camels to humans, therefore, may be an effective strategy to control the ongoing MERS-CoV outbreak. Here we show that vaccination with an adjuvanted MERS-CoV Spike protein subunit vaccine confers complete protection from MERS-CoV disease in alpaca and results in reduced and delayed viral shedding in the upper airways of dromedary camels. Protection in alpaca correlates with high serum neutralizing antibody titers. Lower titers of serum neutralizing antibodies correlate with delayed and significantly reduced shedding in the nasal turbinates of dromedary camels. Together, these data indicate that induction of robust neutralizing humoral immune responses by vaccination of naïve animals reduces shedding that potentially could diminish the risk of zoonotic transmission.

Keywords: MERS-CoV; One Health; camels; vaccines.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Vaccine immunogens and neutralizing antibody responses. (A) Schematic representation of the full MERS-CoV spike protein (top) and the S1 subunit used as antigen for vaccination (bottom). (B) Schematic overview of the immunization timeline with the immunization (blue arrows), serum sampling (red triangle), and challenge and euthanasia (black arrows) time points indicated. (C) Neutralizing antibody titers in dromedary camels and alpacas vaccinated with adjuvanted MERS-CoV S1 as determined by PRNT (90% neutralization).

**Figure 2**
Virus shedding in nasal swabs of vaccinated and unvaccinated dromedary camels and alpaca after challenge with MERS-CoV. Nasal swabs were obtained from dromedary camels (A) and alpaca (B) daily after MERS-CoV challenge and virus titers in swabs were determined in a plaque assay. Red bars indicate vaccinated animals and blue bars indicate unvaccinated control animals. A dashed line indicates the detection limit of the assay. Asterisks indicate statistically significant difference between geometric mean titers (p < 0.05).

**Figure 3**
Infectious virus in respiratory tissues of vaccinated and unvaccinated dromedary camels and alpaca after challenge with MERS-CoV. Dromedary camels (A) and alpaca (B) were euthanized on 5 dpi, tissues were collected, and virus titers were determined in a plaque assay. Red bars indicate vaccinated animals and blue bars indicate unvaccinated control animals. A dashed line indicates the detection limit of the assay. Asterisks indicate statistically significant difference between geometric mean titers (** p < 0.01; **** p < 0.0001). L: left; R: right.

**Figure 4**
Histopathological changes in the respiratory tract of vaccinated and unvaccinated dromedary camels after challenge with MERS-CoV. Nasal turbinate, trachea, and lung were collected from vaccinated (A–F; CA3 shown) and unvaccinated control animals (G–L; CA5 shown) on 5 dpi and stained with hematoxylin and eosin (A–C and G–I), or a polyclonal anti-MERS-CoV antibody panels (D–F and J–L). MERS-CoV antigen is visible as a red brown staining in the immunohistochemistry panel. Vaccinated and unvaccinated camel groups displayed multifocal, minimal-to-mild, acute rhinitis. MERS-CoV antigen was primarily detected in the nasal turbinates. Magnification: 400×.

**Figure 5**
Histopathological changes in the respiratory tract of vaccinated and unvaccinated alpaca after challenge with MERS-CoV. Nasal turbinate, trachea, and lung were collected from vaccinated (A–F; A1 shown) and unvaccinated control animals (G–L; A3 shown) on 5 dpi and stained with hematoxylin and eosin (A–C and G–I), or a polyclonal anti-MERS-CoV antibody panels (D–F and J–L). MERS-CoV antigen is visible as a red brown staining in the immunohistochemistry panel. No histopathological changes were observed in the vaccinated alpaca whereas the unvaccinated control alpaca displayed multifocal, minimal-to-mild, acute rhinitis. MERS-CoV antigen was only detected in the nasal turbinates. Magnification: 400×.

See this image and copyright information in PMC

References

1. WHO Middle East Respiratory Syndrome Coronavirus (MERS-CoV) [(accessed on 1 December 2018)]; Available online: http://www.who.int/emergencies/mers-cov/en/
1. Zaki A.M., van Boheemen S., Bestebroer T.M., Osterhaus A.D., Fouchier R.A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012;367:1814–1820. doi: 10.1056/NEJMoa1211721. - DOI - PubMed
1. Alagaili A.N., Briese T., Mishra N., Kapoor V., Sameroff S.C., de Wit E., Munster V.J., Hensley L.E., Zalmout I.S., Kapoor A., et al. Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia. mBio. 2014;5:e00884-14. doi: 10.1128/mBio.01002-14. - DOI - PMC - PubMed
1. Azhar E.I., Hashem A.M., El-Kafrawy S.A., Sohrab S.S., Aburizaiza A.S., Farraj S.A., Hassan A.M., Al-Saeed M.S., Jamjoom G.A., Madani T.A. Detection of the Middle East Respiratory Syndrome Coronavirus Genome in an Air Sample Originating from a Camel Barn Owned by an Infected Patient. mBio. 2014;5:e01450-14. doi: 10.1128/mBio.01450-14. - DOI - PMC - PubMed
1. Chu D.K., Poon L.L., Gomaa M.M., Shehata M.M., Perera R.A., Abu Zeid D., El Rifay A.S., Siu L.Y., Guan Y., Webby R.J., et al. MERS coronaviruses in dromedary camels, Egypt. Emerg. Infect. Dis. 2014;20:1049–1053. doi: 10.3201/eid2006.140299. - DOI - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Grants and funding

1ZIAAI001179-02/Division of Intramural Research, National Institute of Allergy and Infectious Diseases/International

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

Affiliations

Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources