Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine.
A safe and effective vaccine against RSV remains an important unmet public health need. Intranasally (IN) delivered live-attenuated vaccines represent the most extensively studied approach for immunization of RSV-naïve infants and children, however, achieving an effective balance of attenuation and...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6007926?pdf=render |
| _version_ | 1818172163901882368 |
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| author | Rachel Groppo Joshua DiNapoli Kwang Il Jeong Michael Kishko Nicholas Jackson Harold Kleanthous Simon Delagrave Linong Zhang Mark Parrington |
| author_facet | Rachel Groppo Joshua DiNapoli Kwang Il Jeong Michael Kishko Nicholas Jackson Harold Kleanthous Simon Delagrave Linong Zhang Mark Parrington |
| author_sort | Rachel Groppo |
| collection | DOAJ |
| description | A safe and effective vaccine against RSV remains an important unmet public health need. Intranasally (IN) delivered live-attenuated vaccines represent the most extensively studied approach for immunization of RSV-naïve infants and children, however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we report pre-clinical immunogenicity and efficacy data utilizing a live-attenuated vaccine candidate, RGΔM2-2, which was obtained by deleting the M2-2 open reading frame from the genome of the MSA1 clinical isolate. Intramuscular (IM) administration of RGΔM2-2 in cotton rats induced immunity and protective efficacy that was comparable to that induced by intranasal (IN) immunization. In contrast, the protective efficacy of RGΔM2-2 delivered by the IM route to African green monkeys was substantially reduced as compared to the efficacy following IN administration, despite comparable levels of serum neutralizing antibodies. This result suggests that mucosal immunity may play an important role in RSV protection. The RGΔM2-2 vaccine also demonstrated different attenuation profiles when tested in cotton rats, non-human primates, and a human airway epithelial (HAE) cell model. The data suggest RGΔM2-2 is less attenuated than a similarly designed vaccine candidate constructed on the A2 genetic background. These findings have important implications with regard to both the design and the preclinical safety testing of live-attenuated vaccines. |
| first_indexed | 2024-12-11T19:08:15Z |
| format | Article |
| id | doaj.art-c509bc1f44d047088567bdb72d101f19 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T19:08:15Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c509bc1f44d047088567bdb72d101f192022-12-22T00:53:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019945210.1371/journal.pone.0199452Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine.Rachel GroppoJoshua DiNapoliKwang Il JeongMichael KishkoNicholas JacksonHarold KleanthousSimon DelagraveLinong ZhangMark ParringtonA safe and effective vaccine against RSV remains an important unmet public health need. Intranasally (IN) delivered live-attenuated vaccines represent the most extensively studied approach for immunization of RSV-naïve infants and children, however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we report pre-clinical immunogenicity and efficacy data utilizing a live-attenuated vaccine candidate, RGΔM2-2, which was obtained by deleting the M2-2 open reading frame from the genome of the MSA1 clinical isolate. Intramuscular (IM) administration of RGΔM2-2 in cotton rats induced immunity and protective efficacy that was comparable to that induced by intranasal (IN) immunization. In contrast, the protective efficacy of RGΔM2-2 delivered by the IM route to African green monkeys was substantially reduced as compared to the efficacy following IN administration, despite comparable levels of serum neutralizing antibodies. This result suggests that mucosal immunity may play an important role in RSV protection. The RGΔM2-2 vaccine also demonstrated different attenuation profiles when tested in cotton rats, non-human primates, and a human airway epithelial (HAE) cell model. The data suggest RGΔM2-2 is less attenuated than a similarly designed vaccine candidate constructed on the A2 genetic background. These findings have important implications with regard to both the design and the preclinical safety testing of live-attenuated vaccines.http://europepmc.org/articles/PMC6007926?pdf=render |
| spellingShingle | Rachel Groppo Joshua DiNapoli Kwang Il Jeong Michael Kishko Nicholas Jackson Harold Kleanthous Simon Delagrave Linong Zhang Mark Parrington Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine. PLoS ONE |
| title | Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine. |
| title_full | Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine. |
| title_fullStr | Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine. |
| title_full_unstemmed | Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine. |
| title_short | Effect of genetic background and delivery route on the preclinical properties of a live attenuated RSV vaccine. |
| title_sort | effect of genetic background and delivery route on the preclinical properties of a live attenuated rsv vaccine |
| url | http://europepmc.org/articles/PMC6007926?pdf=render |
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