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Influenza H1N1pdm-specific maternal antibodies offer limited protection against wild-type virus replication and influence influenza vaccination in ferrets.

ABSTRACT: OBJECTIVE:The objective was to study passively acquired influenza H1N1 pandemic (H1N1pdm) maternal antibody kinetics and its impact on subsequent influenza infection and vaccination in ferrets during an outbreak of the H1N1pdm. DESIGN AND MAIN OUTCOME MEASURES:Infectivity of the H1N1pdm in the respiratory tract of ferrets was compared with the previous seasonal A/South Dakota/6/2007 (SD07, H1N1). Influenza-specific antibodies were quantitated and antibody-mediated protection against the homologous and heterologous H1N1 virus challenge infection was determined. RESULTS:H1N1pdm virus was approximately 10 times more infectious than SD07 in ferrets, replicated to higher viral titers in the upper respiratory tract and shed for a longer duration. Influenza-specific antibodies after natural infection persisted much longer in the circulation than passively acquired maternal antibodies. The protection conferred by the maternal antibodies was limited to the homologous virus strain and was ineffective against SD07 and H3N2 virus. Serum antibodies from maternal transmission or passive transfer interfered with homologous vaccine strain-mediated antibody responses in the ferret. A booster immunization was required to elicit a high level of antibody. CONCLUSIONS:The findings support the rationale for a prime and boost immunization strategy in young children in whom maternal antibodies are present.

SUBMITTER: Suguitan AL

PROVIDER: S-EPMC4186464 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Influenza H1N1pdm-specific maternal antibodies offer limited protection against wild-type virus replication and influence influenza vaccination in ferrets.

Suguitan Amorsolo L AL Zengel James R JR Jacobson Scott S Gee Stephanie S Cetz Janet J Cha Paulyn P Chen Zhongying Z Broome Rosemary R Jin Hong H

Influenza and other respiratory viruses 20140301 2

<h4>Objective</h4>The objective was to study passively acquired influenza H1N1 pandemic (H1N1pdm) maternal antibody kinetics and its impact on subsequent influenza infection and vaccination in ferrets during an outbreak of the H1N1pdm.<h4>Design and main outcome measures</h4>Infectivity of the H1N1pdm in the respiratory tract of ferrets was compared with the previous seasonal A/South Dakota/6/2007 (SD07, H1N1). Influenza-specific antibodies were quantitated and antibody-mediated protection again ...[more]

PMID: 24734293

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Project description:The strength and breadth of an individual's antibody repertoire is an important predictor of their response to influenza infection or vaccination. Although progress has been made in understanding qualitatively how repeated exposures shape the antibody mediated immune response, quantitative understanding remains limited. We developed a set of mathematical models describing short-term antibody kinetics following influenza infection or vaccination and fit them to haemagglutination inhibition (HI) titres from 5 groups of ferrets which were exposed to different combinations of trivalent inactivated influenza vaccine (TIV with or without adjuvant), A/H3N2 priming inoculation and post-vaccination A/H1N1 inoculation. We fit models with various immunological mechanisms that have been empirically observed but have not previously been included in mathematical models of antibody landscapes, including: titre ceiling effects, antigenic seniority and exposure-type specific cross reactivity. Based on the parameter estimates of the best supported models, we describe a number of key immunological features. We found quantifiable differences in the degree of homologous and cross-reactive antibody boosting elicited by different exposure types. Infection and adjuvanted vaccination generally resulted in strong, broadly reactive responses whereas unadjuvanted vaccination resulted in a weak, narrow response. We found that the order of exposure mattered: priming with A/H3N2 improved subsequent vaccine response, and the second dose of adjuvanted vaccination resulted in substantially greater antibody boosting than the first. Either antigenic seniority or a titre ceiling effect were included in the two best fitting models, suggesting a role for a mechanism describing diminishing antibody boosting with repeated exposures. Although there was considerable uncertainty in our estimates of antibody waning parameters, our results suggest that both short and long term waning were present and would be identifiable with a larger set of experiments. These results highlight the potential use of repeat exposure animal models in revealing short-term, strain-specific immune dynamics of influenza.

Dataset Information

Influenza H1N1pdm-specific maternal antibodies offer limited protection against wild-type virus replication and influence influenza vaccination in ferrets.

Publications

Influenza H1N1pdm-specific maternal antibodies offer limited protection against wild-type virus replication and influence influenza vaccination in ferrets.

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