Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines.
Vaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored "transmissibl...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-04-01
|
| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001580&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849469234893029376 |
|---|---|
| author | Megan E Griffiths Alice Broos Laura M Bergner Diana K Meza Nicolas M Suarez Ana da Silva Filipe Carlos Tello Daniel J Becker Daniel G Streicker |
| author_facet | Megan E Griffiths Alice Broos Laura M Bergner Diana K Meza Nicolas M Suarez Ana da Silva Filipe Carlos Tello Daniel J Becker Daniel G Streicker |
| author_sort | Megan E Griffiths |
| collection | DOAJ |
| description | Vaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored "transmissible" vaccines that deliberately spread among hosts are a potentially transformative, but still theoretical, solution to the challenge of immunising inaccessible wildlife. Progress towards real-world application is frustrated by the absence of frameworks to guide vector selection and vaccine deployment prior to major in vitro and in vivo investments in vaccine engineering and testing. Here, we performed deep sequencing on field-collected samples of Desmodus rotundus betaherpesvirus (DrBHV), a candidate vector for a transmissible vaccine targeting vampire bat-transmitted rabies. We discovered 11 strains of DrBHV that varied in prevalence and geographic distribution across Peru. The phylogeographic structure of DrBHV strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies and identifying geographic areas for field trials where vaccine spread would be naturally contained. Multistrain infections were observed in 79% of infected bats. Resampling of marked individuals over 4 years showed within-host persistence kinetics characteristic of latency and reactivation, properties that might boost individual immunity and lead to sporadic vaccine transmission over the lifetime of the host. Further, strain acquisitions by already infected individuals implied that preexisting immunity and strain competition are unlikely to inhibit vaccine spread. Our results support the development of a transmissible vaccine targeting a major source of human and animal rabies in Latin America and show how genomics can enlighten vector selection and deployment strategies for transmissible vaccines. |
| format | Article |
| id | doaj-art-724cde700c40413f80ce4ab61746e3f2 |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2022-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-724cde700c40413f80ce4ab61746e3f22025-08-20T03:25:34ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-04-01204e300158010.1371/journal.pbio.3001580Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines.Megan E GriffithsAlice BroosLaura M BergnerDiana K MezaNicolas M SuarezAna da Silva FilipeCarlos TelloDaniel J BeckerDaniel G StreickerVaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored "transmissible" vaccines that deliberately spread among hosts are a potentially transformative, but still theoretical, solution to the challenge of immunising inaccessible wildlife. Progress towards real-world application is frustrated by the absence of frameworks to guide vector selection and vaccine deployment prior to major in vitro and in vivo investments in vaccine engineering and testing. Here, we performed deep sequencing on field-collected samples of Desmodus rotundus betaherpesvirus (DrBHV), a candidate vector for a transmissible vaccine targeting vampire bat-transmitted rabies. We discovered 11 strains of DrBHV that varied in prevalence and geographic distribution across Peru. The phylogeographic structure of DrBHV strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies and identifying geographic areas for field trials where vaccine spread would be naturally contained. Multistrain infections were observed in 79% of infected bats. Resampling of marked individuals over 4 years showed within-host persistence kinetics characteristic of latency and reactivation, properties that might boost individual immunity and lead to sporadic vaccine transmission over the lifetime of the host. Further, strain acquisitions by already infected individuals implied that preexisting immunity and strain competition are unlikely to inhibit vaccine spread. Our results support the development of a transmissible vaccine targeting a major source of human and animal rabies in Latin America and show how genomics can enlighten vector selection and deployment strategies for transmissible vaccines.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001580&type=printable |
| spellingShingle | Megan E Griffiths Alice Broos Laura M Bergner Diana K Meza Nicolas M Suarez Ana da Silva Filipe Carlos Tello Daniel J Becker Daniel G Streicker Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines. PLoS Biology |
| title | Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines. |
| title_full | Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines. |
| title_fullStr | Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines. |
| title_full_unstemmed | Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines. |
| title_short | Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines. |
| title_sort | longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001580&type=printable |
| work_keys_str_mv | AT meganegriffiths longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines AT alicebroos longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines AT laurambergner longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines AT dianakmeza longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines AT nicolasmsuarez longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines AT anadasilvafilipe longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines AT carlostello longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines AT danieljbecker longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines AT danielgstreicker longitudinaldeepsequencinginformsvectorselectionandfuturedeploymentstrategiesfortransmissiblevaccines |