tetano
Editor, Senior Moderator
J Infect Dis
. 2024 May 14:jiae241.
doi: 10.1093/infdis/jiae241. Online ahead of print. Hemagglutinin stalk-specific Fc-mediated functions are associated with protection against influenza-illness after seasonal influenza vaccination in pregnant women
Boitumelo M Motsoeneng[SUP] 1 2 [/SUP], Nisha Dhar[SUP] 3 [/SUP], Marta C Nunes[SUP] 3 4 5 [/SUP], Florian Krammer[SUP] 6 7 8 [/SUP], Shabir A Madhi[SUP] 3 4 9 [/SUP], Penny L Moore[SUP] 1 2 10 [/SUP], Simone I Richardson[SUP] 1 2 [/SUP]
Affiliations
Background: Several influenza vaccine candidates aim to elicit antibodies against the conserved hemagglutinin stalk domain. Understanding the protective mechanism of these antibodies, which mediate broad neutralization and Fc-mediated functions, following seasonal vaccination is critical.
Methods: Plasma samples were obtained from a subset of pregnant women living with or without HIV-1 enrolled in a randomised trial (138 trivalent inactivated vaccine [TIV] and 145 placebo recipients). Twenty-three influenza-illness cases were confirmed within 6 months postpartum. We measured H1 stalk-specific antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD) and cellular cytotoxicity (ADCC) at enrolment and 1-month post-vaccination. The association between these Fc-mediated functions and protection against influenza-illness following vaccination was examined using multiple logistic regression analysis and risk reduction thresholds were defined by the score associated with the lowest odds of influenza-illness.
Results: Amongst TIV and placebo recipients, lower H1 stalk-specific ADCP and ADCD activity was detected for participants with confirmed influenza compared with individuals without confirmed influenza-illness 1-month post-vaccination. Pre-existing ADCP scores ≥250 reduced the odds of A/H1N1 infection (odds ratio 0.11; p=0.01) with an 83% likelihood of risk reduction. Following TIV, ADCD scores of ≥25 and ≥15 significantly reduced the odds against A/H1N1 (0.10; p=0.01) and non-group 1 (0.06; p=0.0004) influenza virus infections, respectively. These ADCD scores were associated with >84% likelihood of risk reduction. H1 stalk-specific ADCC potential was not associated with protection against influenza-illness.
Conclusion: H1 stalk-specific ADCD correlates with protection against influenza-illness following influenza vaccination during pregnancy. These findings provide insight into the protective mechanisms of HA stalk antibodies.
Keywords: Fc effector functions; hemagglutinin stalk; influenza; pregnancy; protection; seasonal influenza vaccine.
. 2024 May 14:jiae241.
doi: 10.1093/infdis/jiae241. Online ahead of print. Hemagglutinin stalk-specific Fc-mediated functions are associated with protection against influenza-illness after seasonal influenza vaccination in pregnant women
Boitumelo M Motsoeneng[SUP] 1 2 [/SUP], Nisha Dhar[SUP] 3 [/SUP], Marta C Nunes[SUP] 3 4 5 [/SUP], Florian Krammer[SUP] 6 7 8 [/SUP], Shabir A Madhi[SUP] 3 4 9 [/SUP], Penny L Moore[SUP] 1 2 10 [/SUP], Simone I Richardson[SUP] 1 2 [/SUP]
Affiliations
- PMID: 38743692
- DOI: 10.1093/infdis/jiae241
Background: Several influenza vaccine candidates aim to elicit antibodies against the conserved hemagglutinin stalk domain. Understanding the protective mechanism of these antibodies, which mediate broad neutralization and Fc-mediated functions, following seasonal vaccination is critical.
Methods: Plasma samples were obtained from a subset of pregnant women living with or without HIV-1 enrolled in a randomised trial (138 trivalent inactivated vaccine [TIV] and 145 placebo recipients). Twenty-three influenza-illness cases were confirmed within 6 months postpartum. We measured H1 stalk-specific antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD) and cellular cytotoxicity (ADCC) at enrolment and 1-month post-vaccination. The association between these Fc-mediated functions and protection against influenza-illness following vaccination was examined using multiple logistic regression analysis and risk reduction thresholds were defined by the score associated with the lowest odds of influenza-illness.
Results: Amongst TIV and placebo recipients, lower H1 stalk-specific ADCP and ADCD activity was detected for participants with confirmed influenza compared with individuals without confirmed influenza-illness 1-month post-vaccination. Pre-existing ADCP scores ≥250 reduced the odds of A/H1N1 infection (odds ratio 0.11; p=0.01) with an 83% likelihood of risk reduction. Following TIV, ADCD scores of ≥25 and ≥15 significantly reduced the odds against A/H1N1 (0.10; p=0.01) and non-group 1 (0.06; p=0.0004) influenza virus infections, respectively. These ADCD scores were associated with >84% likelihood of risk reduction. H1 stalk-specific ADCC potential was not associated with protection against influenza-illness.
Conclusion: H1 stalk-specific ADCD correlates with protection against influenza-illness following influenza vaccination during pregnancy. These findings provide insight into the protective mechanisms of HA stalk antibodies.
Keywords: Fc effector functions; hemagglutinin stalk; influenza; pregnancy; protection; seasonal influenza vaccine.