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A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Antibody function predicts viral control in newborn monkeys immunised with an influenza virus HA stem nanoparticle
Kali F Crofts1,2, Beth C Holbrook1, Courtney L Page1
1Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Insights
A novel universal influenza vaccine (H1ssF) shows promise for infants. Newborn monkeys developed functional antibodies, but viral clearance varied, highlighting the need for potent neutralizing and phagocytic responses.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Current influenza vaccines require annual updates and are not approved for infants under 6 months.
- There is a critical need for a universal influenza vaccine offering protection to vulnerable young infants.
Purpose of the Study:
- To evaluate the efficacy of a ferritin nanoparticle universal influenza vaccine (H1ssF) in newborn African green monkeys (AGM).
- To assess the ability of H1ssF, containing the hemagglutinin (HA) stem region and adjuvanted with AddaVax, to induce protective immune responses in infant non-human primates.
Main Methods:
- Newborn AGM were vaccinated with the H1ssF vaccine adjuvanted with AddaVax.
- Following vaccination, animals were challenged with the H1N1 Ca09 influenza virus.
- Humoral immune responses, including HA stem-specific IgG, neutralizing antibodies, and antibody-dependent cellular phagocytosis (ADCP) activity, were measured.
Main Results:
- Vaccinated newborn AGM exhibited robust HA stem-specific IgG antibody responses.
- Despite high antibody levels, viral loads in the lungs post-challenge showed variability among individuals.
- Viral clearance was found to correlate with the presence of antibodies possessing both neutralizing and ADCP activities.
Conclusions:
- Newborn AGM can generate functional HA stem-specific antibodies in response to H1ssF+AddaVax vaccination.
- The study supports further investigation of H1ssF as a potential universal influenza vaccine for infants.
- The findings underscore the importance of antibody quality, including neutralizing and ADCP functions, for effective viral clearance.
Abstract:
The lack of an approved influenza vaccine for infants <6 months, coupled with the requirement for annual updates of current vaccines, warrants the development of a universal vaccine that can confer protection in young infants. Here we test the ability of a ferritin nanoparticle universal influenza vaccine (H1ssF) containing the stem region of hemagglutinin (HA) adjuvanted with AddaVax to elicit responses in newborn African green monkeys (AGM). Vaccinated newborns show robust HA stem-specific IgG responses but, despite the high antibody levels, viral load in the lung following H1N1 Ca09 challenge is variable among animals. Further analysis indicates that viral clearance is correlated with the presence of antibodies with neutralizing and antibody-dependent cellular phagocytosis activity. Our findings show that newborn AGM can generate functional HA stem-specific antibodies for viral clearance following vaccination with H1ssF+AddaVax and support further investigation of H1ssF as a universal vaccine for this vulnerable human population.
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