Preclinical Evaluation of a Newcastle Disease Virus-Vectored Intranasal SARS-CoV-2 Vaccine

  1. Manolo Fernandez Díaz
  2. Katherine Calderón
  3. Aldo Rojas-Neyra
  4. Vikram N. Vakharia
  5. Ricardo Choque-Guevara
  6. Angela Montalvan
  7. Astrid Poma-Acevedo
  8. Dora Rios-Matos
  9. Andres Agurto- Arteaga
  10. Maria de Grecia Cauti-Mendoza
  11. Norma Perez-Martinez
  12. Gisela Isasi-Rivas
  13. Luis Tataje-Lavanda
  14. Yacory Sernaque-Aguilar
  15. Freddy Ygnacio-Aguirre
  16. Manuel Criollo-Orozco
  17. Edison Huaccachi-Gonzalez
  18. Elmer Delgado-Ccancce
  19. Doris Villanueva-Pérez
  20. Ricardo Montesinos-Millan
  21. Kristel Gutiérrez-Manchay
  22. Katherine Pauyac-Antezana
  23. Ingrid Ramirez-Ortiz
  24. Stefany Quiñones-Garcia
  25. Yudith Cauna-Orocollo
  26. Katherine Vallejos-Sánchez
  27. Angela Rios-Angulo
  28. Dennis Núñez-Fernández
  29. Mario I. Salguedo-Bohorquez
  30. Julio Ticona
  31. Manolo Fernández-Sánchez
  32. Eliana Icochea
  33. Luis Guevara-Sarmiento
  34. Mirko Zimic
  35. COVID-19 Working Group in Perú.

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

The COVID-19 pandemic has claimed the lives of millions of people. Vaccination is a critical tool for the control of transmission; however, the recent emergence of potentially vaccine-resistant variants renders it important to have a range of vaccines types. It is desirable that vaccines are safe, effective, easy to administer and store, and inexpensive to produce. Newcastle disease virus (NDV), responsible for respiratory disease in chickens, has no pathogenic homologue in humans. We developed two types of NDV-vectored candidate vaccines, and evaluated them in a SARS-CoV-2 challenge in hamsters. Vaccinations resulted in generation of neutralizing antibodies, prevented lung damage, and reduced viral load and viability. In conclusion, our NDV-based vaccine candidate performed well in a SARS-CoV-2 challenge and warrants evaluation in a Phase I human clinical trial. This candidate represents a promising tool in the fight against COVID-19.

Article activity feed

  1. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/7640535.

    A brief overview of the paper and its main findings

    First of all, I would like to thank all authors for their invaluable effort to improve Peruvian scientific research. This study shows the results of the preclinical evaluation of a candidate for the COVID-19 vaccine. This proposal was entirely produced in Peru and used a viral vector, the Newcastle virus, which causes respiratory disease in chickens. The main novelty of this proposal is their administration in an intranasal way.

    Major points

    1. There is interesting the use of Syrian hamsters as a study model. It was announced by various articles mentioning similarities between Syrian hamsters and humans on COVID-19 disease. The response to SARS-CoV-2 infection of these animals usually increases in aged (instead of young) individuals, as happens in humans. In your text, you described the use of younger Golden Syrian hamsters (4-5 weeks old) instead of aged ones as other studies have performed (DOI: 10.1038/s41541-021-00321-8 and 10.1073/pnas.2014468117). Therefore I believe that the age of these animals could influence the interpretation of histopathological results. You may found more information about this on PMC7412213 and PMID32571934 to support you in the discussion section.
    2. In Figure 9A, there is hope to see higher levels (above 80%) of viral isolate for all cases in 2 dpi. There would be interesting to see possible reasons for having hamsters with almost zero percent of viral isolation at that moment. Also, I think it important to see a statistical comparison between 2-5-10 dpi, at least for the most important candidate in your proposal (rLS1-S1-F).
    3. Then in the text, you wrote: "This is consistent with previous studies, which reported that viral load is reduced to undetectable levels by 8 days after infection in the hamster animal model". Today we know that viral load is detectable up to 14 days after infection in Syrian hamsters. I think different factors (as the age and sex of these animals) would intermediate this fluctuation. Probably, you should update this information on your preprint, especially on the discussion.
    4. You also wrote: "Being lyophilized, this vaccine candidate is very stable and can be stored for several months at 4-8⁰C". However, I think there is not sufficient evidence to say this by your western blot with products stored up to 50 days. You could attach results of the biological effect of previously-stored vaccine candidates. Also, you may consider testing candidate vaccines stored for more than 2 months.

     

    Minor points

    1. In a general view, I suggest showing more technical details, such as information about qPCR efficiency curves (or efficiency ranges) for all studied genes.
  2. Version published to 10.21203/rs.3.rs-420780/v1 on Research Square