Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2-2 is Highly Immunogenic in Children

Abstract Background Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication. Methods RSV-seronegative children ages 6–24 mo...

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Published in:The Journal of infectious diseases 2018-04, Vol.217 (9), p.1347-1355
Main Authors: McFarland, Elizabeth J, Karron, Ruth A, Muresan, Petronella, Cunningham, Coleen K, Valentine, Megan E, Perlowski, Charlotte, Thumar, Bhagvanji, Gnanashanmugam, Devasena, Siberry, George K, Schappell, Elizabeth, Barr, Emily, Rexroad, Vivian, Yogev, Ram, Spector, Stephen A, Aziz, Mariam, Patel, Nehali, Cielo, Mikhaela, Luongo, Cindy, Collins, Peter L, Buchholz, Ursula J
Format: Article
Language:English
Subjects:
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Double-Blind Method
Editor's Choice
Female
Humans
Infant
Major and Brief Reports
Male
Respiratory Syncytial Virus Infections - prevention & control
Respiratory Syncytial Virus Vaccines - immunology
Respiratory Syncytial Virus, Human - genetics
Vaccines, Attenuated - immunology
Viral Proteins - genetics
Virus Replication
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Summary:Abstract Background Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication. Methods RSV-seronegative children ages 6–24 months received a single intranasal dose of 105 plaque forming units (PFU) of LIDΔM2-2 (n = 20) or placebo (n = 9) (NCT02237209, NCT02040831). RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. During the following RSV season, participants were monitored for respiratory illness and pre- and post-RSV season serum antibodies. Results Vaccine virus was shed by 95% of vaccinees (median peak titers of 3.8 log10 PFU/mL by quantitative culture and 6.3 log10 copies/mL by PCR); 90% had ≥4-fold rise in serum neutralizing antibodies. Respiratory symptoms and fever were common in vaccine (95%) and placebo (78%). One vaccinee had grade 2 rhonchi concurrent with vaccine shedding, rhinovirus, and enterovirus. Eight of 19 vaccinees versus 2 of 9 placebo recipients had substantially increased RSV antibody titers after the RSV season without medically attended RSV disease, indicating anamnestic vaccine responses to wild-type RSV without significant illness. Conclusion LIDΔM2-2 had excellent infectivity and immunogenicity, encouraging further study of vaccine candidates attenuated by M2-2 deletion. Clinical Trials Registration NCT02237209, NCT02040831. The live respiratory syncytial virus (RSV) vaccine LIDΔM2-2, attenuated by deletion of the RNA regulatory protein M2-2, had excellent infectivity and immunogenicity in RSV seronegative 6–24-month old children, encouraging further study of vaccine candidates attenuated by M2-2 deletion.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiy040