Background Development of live attenuated influenza vaccines (LAIV) against avian viruses with pandemic potential is an important public health strategy. Methods and Findings We performed open-label trials to evaluate the safety, infectivity, and immunogenicity of H5N1 VN 2004 AA ca and H5N1 HK 2003 AA ca. Each of these vaccines contains a modified H5 hemagglutinin and unmodified N1 neuraminidase from the respective wild-type (wt) parent virus and the six internal protein gene segments of the A/Ann Arbor/6/60 cold-adapted (ca) master donor virus. The H5N1 VN 2004 AA ca vaccine virus was evaluated at dosages of 106.7 TCID50 and 107.5 TCID50, and the H5N1 HK 2003 AA ca vaccine was evaluated at a dosage of 107.5 TCID50. Two doses were administered intranasally to healthy adults in isolation at 4 to 8 week intervals. Vaccine safety was assessed through daily examinations and infectivity was assessed by viral culture and by realtime reverse transcription-polymerase chain reaction testing of nasal wash (NW) specimens. Immunogenicity was assessed by measuring hemagglutination-inhibition (HI) antibodies, neutralizing antibodies, and IgG or IgA antibodies to recombinant (r)H5 VN 2004 hemagglutinin (HA) in serum or NW. Fifty-nine participants were enrolled: 21 received 106.7 TCID50 and 21 received 107.5 TCID50 of H5N1 VN 2004 AA ca and 17 received H5N1 HK 2003 AA ca. Shedding of vaccine virus was minimal, as were HI and neutralizing antibody responses. Fifty-two percent of recipients of 107.5 TCID50 of H5N1 VN 2004 AA ca developed a serum IgA response to rH5 VN 2004 HA. Conclusions The live attenuated H5N1 VN 2004 and HK 2003 AA ca vaccines bearing avian H5 HA antigens were very restricted in replication and were more attenuated than seasonal LAIV bearing human H1, H3 or B HA antigens. The H5N1 AA ca LAIV elicited serum ELISA antibody but not HI or neutralizing antibody responses in healthy adults. (ClinicalTrials.gov Identifiers: NCT00347672 and NCT00488046).

Development of live attenuated influenza vaccines (LAIV) against avian strains with pandemic potential is an important public-health strategy. Either 1 or 2 107-TCID50 doses of H9N2 LAIV A/chicken/Hong Kong/G9/97 were administered intranasally to 50 adults in isolation; 41 participants were H9N2 seronegative, 24 of whom received 2 doses. The vaccine was well tolerated; vaccine shedding was minimal. After 2 doses, 92% of H9-seronegative participants had ≥4-fold increases in hemagglutination-inhibition antibody, and 79% had ≥4-fold increases in neutralizing antibody; 100% had responses detected by at least 1 assay. Although replication of the H9N2 LAIV was restricted, 2 doses were immunogenic in H9N2-seronegative adults.

We assessed the agreement between rectal and noninvasive temporal artery temperature measurements in infants and children. We also evaluated the temple thermometer as a screening tool for rectal fever in this age group. Finally, we compared the performance of parents with that of nurses in using the temple thermometer. The 95% limits of agreement between the difference in rectal and average temple temperature were -1.03 and +1.52 degrees C. Mean temple temperatures obtained by parents and by nurses were similar (95% limits of agreement, -0.6 degrees C to +0.7 degrees C). A maximum temple temperature cutoff of 37.2 degrees C (99.0 degrees F) distinguished children with rectal fever of > or =38.0 degrees C with 91% sensitivity and 53% specificity. A cutoff of 37.8 degrees C (100.0 degrees F) distinguished moderate rectal fevers (> or =38.5 degrees C) with 97% sensitivity and 84% specificity. A cutoff of 38.3 degrees C (101.0 degrees F) distinguished a high rectal fever (> or =39.0 degrees C) with a sensitivity of 95% and specificity of 95%. In conclusion, temple temperatures do not reliably predict rectal temperatures, but the temple thermometer can be used as an effective screen for clinically important rectal fever in children 3-24 months old. The findings do not support use of temple temperatures to screen young infants for rectal fever > or =38.0 degrees C. Temperatures obtained by parents were comparable to those obtained by nurses.

Human parainfluenza virus type 3 (HPIV3) is an important cause of lower respiratory tract illness in children, yet a licensed vaccine or antiviral drug is not available. We evaluated the safety, tolerability, infectivity, and immunogenicity of two intranasal, live-attenuated HPIV3 vaccines, designated rHPIV3-NB and rB/HPIV3, that were cDNA-derived chimeras of HPIV3 and bovine PIV3 (BPIV3). These were evaluated in adults, HPIV3 seropositive children, and HPIV3 seronegative children. A total of 112 subjects participated in these studies. Both rB/HPIV3 and rHPIV3-NB were highly restricted in replication in adults and seropositive children but readily infected seronegative children, who shed mean peak virus titers of 102.8 vs. 103.7 pfu/mL, respectively. Although rB/HPIV3 was more restricted in replication in seronegative children than rHPIV3-NB, it induced significantly higher titers of hemagglutination inhibition (HAI) antibodies against HPIV3. Taken together, these data suggest that the rB/HPIV3 vaccine is the preferred candidate for further clinical development.