Effects of Aging on Influenza Virus Infection Dynamics

Hernandez‐Vargas, Esteban A.; Wilk, Esther; Canini, Laetitia; Toapanta, Franklin R.; Binder, Sebastian C.; Uvarovskii, Alexey; Ross, Ted M.; Guzmán, Carlos A.; Perelson, Alan S.; Meyer‐Hermann, Michael

doi:10.1128/jvi.03644-13

Cited by 129 publications

(136 citation statements)

References 59 publications

Supporting

Mentioning

131

Contrasting

Order By: Relevance

“…Of course, none of these models have a lifetime of accumulated experience with influenza virus antigens when vaccinated or challenged in old age. Nonetheless, aged mice have been widely used to study age-related changes in immune responses to influenza virus challenge (19)(20)(21), as well as new influenza vaccination strategies for the elderly (22)(23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response

Hodgins

Yam

Winter

et al. 2017

Clin Vaccine Immunol

View full text Add to dashboard Cite

Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5-to 8-week-old) and aged (16-to 20-month-old) female BALB/c mice received a single 3-g dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the splitvirion vaccine.KEYWORDS aged-mouse model, influenza, virus-like particles (VLPs), plant-made vaccines A ccording to the World Health Organization, influenza epidemics account for 250,000 to 500,000 deaths worldwide every year (http://www.who.int/mediacentre/factsheets/ fs211/en/). Although vaccines are widely recommended to protect against influenza, the elderly often respond poorly, in part due to prior experience with influenza virus antigens (Ag) (1), but also as a result of immunosenescence (2). The latter affects both innate and adaptive immune responses and has broad implications for both natural infection and vaccination (1, 2).Influenza vaccines for adults are administered by either intramuscular (i.m.) or intradermal injection of detergent-split virions at a fixed dose of 15 g hemagglutinin (HA)/strain (3). These vaccines typically elicit strong antibody responses in healthy young adults and achieve vaccine efficacy (VE) that varies between strains and years but averages 50 to 60% (4). These formulations work less well in the elderly (5

show abstract

Section: Discussionmentioning

confidence: 99%

A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response

Hodgins

Yam

Winter

et al. 2017

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…However, immune functions decline due to aging, a phenomenon called immunosenescence [83], and this leads to influenza having more serious health consequences in the elderly. While not modeled in humans, a recent viral kinetic model analyzed the effect of aging on innate and adaptive immune responses in the context of influenza viral kinetics in mice [84]. …”

Section: Modeling Hcv Viral Kineticsmentioning

confidence: 99%

Viral kinetic modeling: state of the art

Canini

Perelson

2014

J Pharmacokinet Pharmacodyn

Self Cite

View full text Add to dashboard Cite

Viral kinetic modeling has led to increased understanding of the within host dynamics of viral infections and the effects of therapy. Here we review recent developments in the modeling of viral infection kinetics with emphasis on two infectious diseases: hepatitis C and influenza. We review how viral kinetic modeling has evolved from simple models of viral infections treated with a drug or drug cocktail with an assumed constant effectiveness to models that incorporate drug pharmacokinetics and pharmacodynamics, as well as phenomenological models that simply assume drugs have time varying-effectiveness. We also discuss multiscale models that include intracellular events in viral replication, models of drug-resistance, models that include innate and adaptive immune responses and models that incorporate cell-to-cell spread of infection. Overall, viral kinetic modeling has provided new insights into the understanding of the disease progression and the modes of action of several drugs. We expect that viral kinetic modeling will be increasingly used in the coming years to optimize drug regimens in order to improve therapeutic outcomes and treatment tolerability for infectious diseases.

show abstract

“…One of the most significant risk factor for influenza infection is age (Lee et al, 2012;Hernandez-Vargas et al, 2014), multi-organ failure in severe cases (Yamane et al, 2014) and death.…”

Section: Introduction------------------------------------------------mentioning

confidence: 99%