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Randomized Controlled Trial
. 2024 Feb 14;229(2):346-354.
doi: 10.1093/infdis/jiad281.

Evaluation of the Live-Attenuated Intranasal Respiratory Syncytial Virus (RSV) Vaccine RSV/6120/ΔNS2/1030s in RSV-Seronegative Young Children

Ruth A Karron  1 , Cindy Luongo  2 , Suzanne Woods  1 , Jennifer Oliva  1 , Peter L Collins  2 , Ursula J Buchholz  2 ; RSVPed Team
Collaborators, Affiliations
Randomized Controlled Trial

Evaluation of the Live-Attenuated Intranasal Respiratory Syncytial Virus (RSV) Vaccine RSV/6120/ΔNS2/1030s in RSV-Seronegative Young Children

Ruth A Karron et al. J Infect Dis. .

Abstract

Background: Respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory illness (LRI) and a vaccine for immunization of children is needed. RSV/6120/ΔNS2/1030s is a cDNA-derived live-vaccine candidate attenuated by deletion of the interferon antagonist NS2 gene and the genetically stabilized 1030s missense polymerase mutation in the polymerase, conferring temperature sensitivity.

Methods: A single intranasal dose of RSV/6120/ΔNS2/1030s was evaluated in a double-blind, placebo-controlled trial (vaccine to placebo ratio, 2:1) at 105.7 plaque-forming units (PFU) in 15 RSV-seropositive 12- to 59-month-old children, and at 105 PFU in 30 RSV-seronegative 6- to 24-month-old children.

Results: RSV/6120/ΔNS2/1030s infected 100% of RSV-seronegative vaccinees and was immunogenic (geometric mean RSV plaque-reduction neutralizing antibody titer [RSV-PRNT], 1:91) and genetically stable. Mild rhinorrhea was detected more frequently in vaccinees (18/20 vaccinees vs 4/10 placebo recipients, P = .007), and LRI occurred in 1 vaccinee during a period when only vaccine virus was detected. Following the RSV season, 5 of 16 vaccinees had ≥4-fold rises in RSV-PRNT with significantly higher titers than 4 of 10 placebo recipients with rises (1:1992 vs 1:274, P = .02). Thus, RSV/6120/ΔNS2/1030s primed for substantial anamnestic neutralizing antibody responses following naturally acquired RSV infection.

Conclusions: RSV/6120/ΔNS2/1030s is immunogenic and genetically stable in RSV-seronegative children, but the frequency of rhinorrhea in vaccinees exceeded that in placebo recipients.

Clinical trials registration: NCT03387137.

Keywords: RSV; intranasal vaccine; live-attenuated; pediatric; vaccine.

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Conflict of interest statement

Potential conflicts of interest . C. L., P. L. C., and U. J. B. are inventors on US patents pertaining to this vaccine candidate and its attenuating mutations. R. A. K. receives additional grant funding from Sanofi through her institution. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Screening, enrollment, and follow-up of respiratory syncytial virus (RSV)-seropositive children and RSV-seronegative children in the phase 1 clinical trial of the RSV/6120/ΔNS2/1030s vaccine. As described in the “Methods” section, enrollment of RSV-seronegative children occurred following a satisfactory review of safety data from RSV-seropositive children.
Figure 2.
Figure 2.
Proportions of RSV-seronegative vaccinees and placebo recipients with indicated illnesses during the first 28 days postvaccination. Vaccinees are shown in black; placebo recipients are shown in gray. Abbreviations: LRI, lower respiratory illness; RSV, respiratory syncytial virus.
Figure 3.
Figure 3.
Individual daily titers of vaccine virus shed by RSV-seronegative recipients of 105.0 PFU of vaccine, with symbols representing titers by culture (A) and by RT-qPCR (B). Peak titers from individual vaccinees are shown as diamonds, and means are indicated by a continuous line. Culture-negative samples were assigned a titer of 0.5 log10 PFU/mL, and RT-qPCR-negative samples were assigned a titer of 1.7 log10 copies/mL, indicated by the dotted line in A and B, Abbreviations: PFU, plaque-forming unit; RSV, respiratory syncytial virus; RT-qPCR, reverse transcription-quantitative polymerase chain reaction.
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