Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination

ABSTRACT Obesity is a risk factor for developing severe influenza virus infection, making vaccination of utmost importance for this high-risk population. However, vaccinated obese animals and adults have decreased neutralizing antibody responses. In these studies, we tested the hypothesis that the a...

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Autores principales:	Erik A. Karlsson, Tomer Hertz, Cydney Johnson, Andrew Mehle, Florian Krammer, Stacey Schultz-Cherry
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/37aa348663ec4e468171a538f69e4f15
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spelling	oai:doaj.org-article:37aa348663ec4e468171a538f69e4f152021-11-15T15:50:19ZObesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination10.1128/mBio.01144-162150-7511https://doaj.org/article/37aa348663ec4e468171a538f69e4f152016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01144-16https://doaj.org/toc/2150-7511ABSTRACT Obesity is a risk factor for developing severe influenza virus infection, making vaccination of utmost importance for this high-risk population. However, vaccinated obese animals and adults have decreased neutralizing antibody responses. In these studies, we tested the hypothesis that the addition of either alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve neutralizing antibody responses and protect obese mice from challenge. Our studies demonstrate that adjuvanted vaccine does increase both neutralizing and nonneutralizing antibody levels compared to vaccine alone. Although obese mice mount significantly decreased virus-specific antibody responses, both the breadth and the magnitude of the responses against hemagglutinin (HA) and neuraminidase (NA) are decreased compared to the responses in lean mice. Importantly, even with a greater than fourfold increase in neutralizing antibody levels, obese mice are not protected against influenza virus challenge and viral loads remain elevated in the respiratory tract. Increasing the antigen dose affords no added protection, and a decreasing viral dose did not fully mitigate the increased mortality seen in obese mice. Overall, these studies highlight that, while the use of an adjuvant does improve seroconversion, vaccination does not fully protect obese mice from influenza virus challenge, possibly due to the increased sensitivity of obese animals to infection. Given the continued increase in the global obesity epidemic, our findings have important implications for public health. IMPORTANCE Vaccination is the most effective strategy for preventing influenza virus infection and is a key component for pandemic preparedness. However, vaccines may fail to provide optimal protection in high-risk groups, including overweight and obese individuals. Given the worldwide obesity epidemic, it is imperative that we understand and improve vaccine efficacy. No work to date has investigated whether adjuvants increase the protective capacity of influenza vaccines in the obese host. In these studies, we show that adjuvants increased the neutralizing and nonneutralizing antibody responses during vaccination of lean and obese mice to levels considered “protective,” and yet, obese mice still succumbed to infection. This vulnerability is likely due to a combination of factors, including the increased susceptibility of obese animals to develop severe and even lethal disease when infected with very low viral titers. Our studies highlight the critical public health need to translate these findings and better understand vaccination in this increasing population.Erik A. KarlssonTomer HertzCydney JohnsonAndrew MehleFlorian KrammerStacey Schultz-CherryAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Erik A. Karlsson Tomer Hertz Cydney Johnson Andrew Mehle Florian Krammer Stacey Schultz-Cherry Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination
description	ABSTRACT Obesity is a risk factor for developing severe influenza virus infection, making vaccination of utmost importance for this high-risk population. However, vaccinated obese animals and adults have decreased neutralizing antibody responses. In these studies, we tested the hypothesis that the addition of either alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve neutralizing antibody responses and protect obese mice from challenge. Our studies demonstrate that adjuvanted vaccine does increase both neutralizing and nonneutralizing antibody levels compared to vaccine alone. Although obese mice mount significantly decreased virus-specific antibody responses, both the breadth and the magnitude of the responses against hemagglutinin (HA) and neuraminidase (NA) are decreased compared to the responses in lean mice. Importantly, even with a greater than fourfold increase in neutralizing antibody levels, obese mice are not protected against influenza virus challenge and viral loads remain elevated in the respiratory tract. Increasing the antigen dose affords no added protection, and a decreasing viral dose did not fully mitigate the increased mortality seen in obese mice. Overall, these studies highlight that, while the use of an adjuvant does improve seroconversion, vaccination does not fully protect obese mice from influenza virus challenge, possibly due to the increased sensitivity of obese animals to infection. Given the continued increase in the global obesity epidemic, our findings have important implications for public health. IMPORTANCE Vaccination is the most effective strategy for preventing influenza virus infection and is a key component for pandemic preparedness. However, vaccines may fail to provide optimal protection in high-risk groups, including overweight and obese individuals. Given the worldwide obesity epidemic, it is imperative that we understand and improve vaccine efficacy. No work to date has investigated whether adjuvants increase the protective capacity of influenza vaccines in the obese host. In these studies, we show that adjuvants increased the neutralizing and nonneutralizing antibody responses during vaccination of lean and obese mice to levels considered “protective,” and yet, obese mice still succumbed to infection. This vulnerability is likely due to a combination of factors, including the increased susceptibility of obese animals to develop severe and even lethal disease when infected with very low viral titers. Our studies highlight the critical public health need to translate these findings and better understand vaccination in this increasing population.
format	article
author	Erik A. Karlsson Tomer Hertz Cydney Johnson Andrew Mehle Florian Krammer Stacey Schultz-Cherry
author_facet	Erik A. Karlsson Tomer Hertz Cydney Johnson Andrew Mehle Florian Krammer Stacey Schultz-Cherry
author_sort	Erik A. Karlsson
title	Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination
title_short	Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination
title_full	Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination
title_fullStr	Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination
title_full_unstemmed	Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination
title_sort	obesity outweighs protection conferred by adjuvanted influenza vaccination
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/37aa348663ec4e468171a538f69e4f15
work_keys_str_mv	AT erikakarlsson obesityoutweighsprotectionconferredbyadjuvantedinfluenzavaccination AT tomerhertz obesityoutweighsprotectionconferredbyadjuvantedinfluenzavaccination AT cydneyjohnson obesityoutweighsprotectionconferredbyadjuvantedinfluenzavaccination AT andrewmehle obesityoutweighsprotectionconferredbyadjuvantedinfluenzavaccination AT floriankrammer obesityoutweighsprotectionconferredbyadjuvantedinfluenzavaccination AT staceyschultzcherry obesityoutweighsprotectionconferredbyadjuvantedinfluenzavaccination
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Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination

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