Table 1.
Clinical Responses, Vaccine Virus Shedding, and Antibody Responses After Administration of rHMPV-Pa or Placebo to Adults and HMPV-Seropositive and -Seronegative Children
| Subject | Dose (log10 TCID50/mL) | No. of Subjects | Subjects Infected (%)a | Subjects With Indicated Illness (%) | Viral Sheddingb | Serum PRN Ab Response | Serum HMPV IgG Ab Response | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fever | URI | LRI | Cough | OM | Respiratory or Febrile Illness | % Shedding Virus | Peak Titer (log10 PFU/mL) (mean [SD]) | Peak Titer (log10 copies/ mL) (mean [SD]) | Mean of 1/log2 (SD) | ≥4-Fold Rise (%) | Mean of 1/log2 (SD) | ≥4-Fold Rise (%) | ||||||
| Before Vaccine | After Vaccine | Before Vaccine | After Vaccine | |||||||||||||||
| Adults | ||||||||||||||||||
| Vaccine recipientsc | 6.0 | 15 | 0 | 0 | 13 | 7 | 13 | 0 | 13 | 0 | 0.6 (0.0) | 2.1 | 7.7 (0.9) | 7.8 (0.9) | 0 | 13.3 (1.0) | 12.9 (1.4) | 0 |
| Seropositive children | ||||||||||||||||||
| Vaccine recipients | 6.0 | 10 | 20 | 0 | 10 | 0 | 0 | 0 | 10 | 0 | 0.6 (0.0) | 2.1 | 7.8 (1.0) | 7.8 (1.0) | 0 | 12.0 (1.6) | 12.4 (1.7) | 20 |
| Placebo recipients | — | 5 | 0 | 20 | 20 | 0 | 0 | 0 | 40 | 0 | 0.6 (0.0) | 2.1 | 7.7 (0.8) | 7.9 (0.9) | 0 | 11.6 (1.4) | 11.2 (0.9) | 0 |
| Seronegative children | ||||||||||||||||||
| Vaccine recipients | 5.0 | 10 | 30 | 0 | 40 | 0 | 10 | 10 | 50 | 0 | 0.6 (0.0) | 2.1 | 2.3 (0.0) | 2.9 (1.2) | 20 | 4.6 (0.0) | 5.4 (2.2) | 10 |
| 6.0 | 10 | 50 | 10 | 30 | 10 | 20 | 0 | 50 | 20 | 0.6 (0.0) | 3.1 (0.6) | 2.9 (0.9) | 4.1 (1.7) | 30 | 6.3 (2.1) | 8.3 (1.9) | 50 | |
| Placebo recipients | — | 10 | 0 | 10 | 20 | 0 | 0 | 10 | 30 | 0 | 0.6 (0.0) | 2.1 | 2.8 (0.7) | 2.8 (0.7) | 0 | 6.1 (2.4) | 6.3 (2.3) | 0 |
Abbreviations: Ab, antibody; HMPV, human metapneumovirus; LRI, lower respiratory tract illness; OM, otitis media; PFU, plaque-forming units; PR, placebo recipient; PRN, plaque-reduction neutralization; rHMPV-Pa, live attenuated recombinant HMPV vaccine; SD, standard deviation; TCID50, 50% tissue culture infective dose; URI, upper respiratory tract illness; VR, vaccine recipient.
aInfection was defined as a ≥4-fold rise in neutralizing antibody or HMPV F immunoglobulin G antibody titer and/or detection of vaccine virus by culture or RT-qPCR.
bThe limit of detection of vaccine virus by culture was 0.6 log10 PFU/mL, and the limit of detection by real-time quantitative polymerase chain reaction (RT-qPCR) was 2.1 log10 copies/mL. The percentage shedding virus was as detected by culture or RT-qPCR.
cOne VR had wheezing (LRI) associated with recovery of respiratory syncytial virus from her nasal wash fluid sample.