tetano
Editor, Senior Moderator
Lancet Microbe
. 2025 Jan 17:100971.
doi: 10.1016/j.lanmic.2024.100971. Online ahead of print. Interactions between live attenuated influenza vaccine and nasopharyngeal microbiota among children aged 24-59 months in The Gambia: a phase 4, open-label, randomised controlled trial
Chikondi Peno[SUP] 1 [/SUP], Ya Jankey Jagne[SUP] 2 [/SUP], Melanie Clerc[SUP] 3 [/SUP], Carlos Balcazar Lopez[SUP] 3 [/SUP], Edwin P Armitage[SUP] 2 [/SUP], Hadijatou Sallah[SUP] 2 [/SUP], Sainabou Drammeh[SUP] 2 [/SUP], Elina Senghore[SUP] 2 [/SUP], Gabriel Goderski[SUP] 4 [/SUP], Sophie van Tol[SUP] 4 [/SUP], Adam Meijer[SUP] 4 [/SUP], Alicia Ruiz-Rodriguez[SUP] 3 [/SUP], Wouter de Steenhuijsen Piters[SUP] 5 [/SUP], Emma de Koff[SUP] 5 [/SUP], Sheikh Jarju[SUP] 2 [/SUP], Benjamin B Lindsey[SUP] 6 [/SUP], Janko Camara[SUP] 2 [/SUP], Sulayman Bah[SUP] 2 [/SUP], Nuredin I Mohammed[SUP] 2 [/SUP], Beate Kampmann[SUP] 7 [/SUP], Ed Clarke[SUP] 2 [/SUP], David H Dockrell[SUP] 3 [/SUP], Thushan I de Silva[SUP] 8 [/SUP], Debby Bogaert[SUP] 9 [/SUP]
Affiliations
Background: Live attenuated influenza vaccines (LAIVs) alter nasopharyngeal microbiota in adults. It is poorly understood why LAIV immunogenicity varies across populations, but it could be linked to the microbiome. We aimed to investigate the interactions between intranasal immunisation with LAIV and nasopharyngeal microbiota composition in children from The Gambia.
Methods: We conducted a phase 4, open-label, randomised controlled trial in Sukuta, The Gambia. Children aged 24-59 months with no underlying illness or history of respiratory illness for at least 14 days before recruitment were eligible. Participants were randomly assigned (2:1) by use of a computer-generated sequence in permuted blocks of 15, stratified by sex, to receive trivalent LAIV either on day 0 (intervention group) or after active follow-up at day 21 (control group). The investigator team was initially masked to block size and randomisation sequence; however, group allocation was later revealed to the team. Microbiome profiles were characterised from nasopharyngeal samples collected from all participants on days 0, 7, and 21 by use of 16S rRNA sequencing. The primary outcomes were the effect of LAIV on nasopharyngeal microbiome profiles on day 7 and day 21, and the association between the nasopharyngeal microbiome at baseline and LAIV-induced mucosal IgA responses at day 21, assessed with permutational ANOVA tests. Asymptomatic respiratory viral co-infection at baseline and year of recruitment (2017 or 2018) were included as covariates. This trial is registered with ClinicalTrials.gov (NCT02972957) and is closed.
Findings: Between Feb 8 and April 12, 2017, and Jan 15 and March 28, 2018, 343 children were screened for eligibility, of whom 220 (64%) children were randomly assigned to the intervention group and 110 (32%) to the control group. 213 (97%) children in the intervention group and 108 (98%) in the control group completed the study and were included in the final analysis. Although we did not observe an independent effect of LAIV on microbial community composition at days 7 or 21, we found that LAIV had an effect dependent on the year of recruitment. LAIV affected microbial community composition in 2018 (R[SUP]2[/SUP] 1·97% [95% CI 0·85-5·94]; p=0·037), but not in 2017 (1·23% [0·49-4·46]; p=0·091). We also found that viral co-infection at baseline had an effect on microbial composition at day 7, regardless of recruitment year (R[SUP]2[/SUP] 1·01% [95% CI 0·28-3·01]; p=0·026). Nasopharyngeal microbial community composition at baseline had no effect on mucosal IgA responses to LAIV administration (R[SUP]2[/SUP] 0·51% [95% CI 0·23-2·49]; p=0·46).
Interpretation: Our findings suggest that the effect of LAIVs on nasopharyngeal microbiota composition in children is modest and temporary; therefore, LAIVs could be used as an intervention to curb influenza in children from low-income and middle-income countries, without causing long-lasting perturbations in nasopharyngeal microbiota. However, nasopharyngeal microbiota at the time of vaccination might not explain the variability observed between individuals in LAIV-induced IgA responses.
Funding: The Wellcome Trust, UK National Institute for Health Research, and Chief Scientist Office Scotland.
. 2025 Jan 17:100971.
doi: 10.1016/j.lanmic.2024.100971. Online ahead of print. Interactions between live attenuated influenza vaccine and nasopharyngeal microbiota among children aged 24-59 months in The Gambia: a phase 4, open-label, randomised controlled trial
Chikondi Peno[SUP] 1 [/SUP], Ya Jankey Jagne[SUP] 2 [/SUP], Melanie Clerc[SUP] 3 [/SUP], Carlos Balcazar Lopez[SUP] 3 [/SUP], Edwin P Armitage[SUP] 2 [/SUP], Hadijatou Sallah[SUP] 2 [/SUP], Sainabou Drammeh[SUP] 2 [/SUP], Elina Senghore[SUP] 2 [/SUP], Gabriel Goderski[SUP] 4 [/SUP], Sophie van Tol[SUP] 4 [/SUP], Adam Meijer[SUP] 4 [/SUP], Alicia Ruiz-Rodriguez[SUP] 3 [/SUP], Wouter de Steenhuijsen Piters[SUP] 5 [/SUP], Emma de Koff[SUP] 5 [/SUP], Sheikh Jarju[SUP] 2 [/SUP], Benjamin B Lindsey[SUP] 6 [/SUP], Janko Camara[SUP] 2 [/SUP], Sulayman Bah[SUP] 2 [/SUP], Nuredin I Mohammed[SUP] 2 [/SUP], Beate Kampmann[SUP] 7 [/SUP], Ed Clarke[SUP] 2 [/SUP], David H Dockrell[SUP] 3 [/SUP], Thushan I de Silva[SUP] 8 [/SUP], Debby Bogaert[SUP] 9 [/SUP]
Affiliations
- PMID: 39832517
- DOI: 10.1016/j.lanmic.2024.100971
Background: Live attenuated influenza vaccines (LAIVs) alter nasopharyngeal microbiota in adults. It is poorly understood why LAIV immunogenicity varies across populations, but it could be linked to the microbiome. We aimed to investigate the interactions between intranasal immunisation with LAIV and nasopharyngeal microbiota composition in children from The Gambia.
Methods: We conducted a phase 4, open-label, randomised controlled trial in Sukuta, The Gambia. Children aged 24-59 months with no underlying illness or history of respiratory illness for at least 14 days before recruitment were eligible. Participants were randomly assigned (2:1) by use of a computer-generated sequence in permuted blocks of 15, stratified by sex, to receive trivalent LAIV either on day 0 (intervention group) or after active follow-up at day 21 (control group). The investigator team was initially masked to block size and randomisation sequence; however, group allocation was later revealed to the team. Microbiome profiles were characterised from nasopharyngeal samples collected from all participants on days 0, 7, and 21 by use of 16S rRNA sequencing. The primary outcomes were the effect of LAIV on nasopharyngeal microbiome profiles on day 7 and day 21, and the association between the nasopharyngeal microbiome at baseline and LAIV-induced mucosal IgA responses at day 21, assessed with permutational ANOVA tests. Asymptomatic respiratory viral co-infection at baseline and year of recruitment (2017 or 2018) were included as covariates. This trial is registered with ClinicalTrials.gov (NCT02972957) and is closed.
Findings: Between Feb 8 and April 12, 2017, and Jan 15 and March 28, 2018, 343 children were screened for eligibility, of whom 220 (64%) children were randomly assigned to the intervention group and 110 (32%) to the control group. 213 (97%) children in the intervention group and 108 (98%) in the control group completed the study and were included in the final analysis. Although we did not observe an independent effect of LAIV on microbial community composition at days 7 or 21, we found that LAIV had an effect dependent on the year of recruitment. LAIV affected microbial community composition in 2018 (R[SUP]2[/SUP] 1·97% [95% CI 0·85-5·94]; p=0·037), but not in 2017 (1·23% [0·49-4·46]; p=0·091). We also found that viral co-infection at baseline had an effect on microbial composition at day 7, regardless of recruitment year (R[SUP]2[/SUP] 1·01% [95% CI 0·28-3·01]; p=0·026). Nasopharyngeal microbial community composition at baseline had no effect on mucosal IgA responses to LAIV administration (R[SUP]2[/SUP] 0·51% [95% CI 0·23-2·49]; p=0·46).
Interpretation: Our findings suggest that the effect of LAIVs on nasopharyngeal microbiota composition in children is modest and temporary; therefore, LAIVs could be used as an intervention to curb influenza in children from low-income and middle-income countries, without causing long-lasting perturbations in nasopharyngeal microbiota. However, nasopharyngeal microbiota at the time of vaccination might not explain the variability observed between individuals in LAIV-induced IgA responses.
Funding: The Wellcome Trust, UK National Institute for Health Research, and Chief Scientist Office Scotland.