Dataset Information

Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women.

ABSTRACT:

Background

Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life.

Methods

In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3) or placebo.

Results

Solicited local adverse events (AEs) were more frequently reported in the RSVPreF3 groups (4%-53.2%) versus placebo (0%-15.9%); most were mild/moderate. Unsolicited AEs were comparably reported among groups. Three serious AEs were reported; none was vaccination-related. Compared with prevaccination values, anti-RSV A neutralizing antibody geometric mean titers and anti-RSVPreF3 immunoglobulin G geometric mean concentrations increased 8- to 14-fold and 12- to 21-fold at day 8 and persisted 5- to 6-fold and 6- to 8-fold higher until day 91 in the RSVPreF3 groups versus 1-fold in placebo. Comparisons at day 8 and day 31 showed that the higher dose levels were significantly more immunogenic than the lowest one.

Conclusions

The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women.

Clinical trials registration

NCT03674177.

SUBMITTER: Schwarz TF

PROVIDER: S-EPMC9200160 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women.

Schwarz Tino F TF Johnson Casey C Grigat Christine C Apter Dan D Csonka Peter P Lindblad Niklas N Nguyen Thi Lien-Anh TL Gao Feng F FF Qian Hui H Tullio Antonella N AN Dieussaert Ilse I Picciolato Marta M Henry Ouzama O

The Journal of infectious diseases 20220601 12

<h4>Background</h4>Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life.<h4>Methods</h4>In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the pre ...[more]

PMID: 34146100

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Project description:UnlabelledAlthough respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log10 total PFU and 2.7 log10 PFU/g of tissue, respectively, compared to those in unvaccinated animals (P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity.ImportanceRSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats.

Dataset Information

Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women.

Background

Methods

Results

Conclusions

Clinical trials registration

Publications

Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women.

Similar Datasets

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