scholarly journals The Power of First Impressions: Can Influenza Imprinting during Infancy Inform Vaccine Design?

Author(s):  
Melissa Rioux ◽  
Mara McNeil ◽  
Magen Francis ◽  
Nicholas Dawe ◽  
Mary Foley ◽  
...  

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 546
Author(s):  
Melissa Rioux ◽  
Mara McNeil ◽  
Magen E. Francis ◽  
Nicholas Dawe ◽  
Mary Foley ◽  
...  

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system, and lack of previous exposure to the virus is thought to synergistically play a role in the increased disease severity in younger age groups. No influenza vaccines are available for those under six months, although maternal influenza immunization is recommended. In children aged six months to two years, vaccine immunogenicity is dampened compared to older children and adults. Unlike older children and adults, the infant immune system has fewer antigen-presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. We contend that by understanding the influenza imprinting event in the context of the infant immune system, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune and respiratory development, current vaccine strategies, and highlights the importance of research into the imprinting event in infant animal models to develop more effective and protective vaccines for all including young children.


2009 ◽  
Vol 53 (4) ◽  
pp. 233-240 ◽  
Author(s):  
Y. Hama ◽  
M. Kurokawa ◽  
M. Imakita ◽  
Y. Yoshida ◽  
T. Shimizu ◽  
...  

2012 ◽  
Vol 7 (3) ◽  
pp. 244-248 ◽  
Author(s):  
Serena Roth ◽  
Sara Whitehead ◽  
Somsak Thamthitiwat ◽  
Malinee Chittaganpitch ◽  
Susan A. Maloney ◽  
...  

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Brad Gilbertson ◽  
Wy Ching Ng ◽  
Simon Crawford ◽  
Jenny L. McKimm-Breschkin ◽  
Lorena E. Brown

ABSTRACT We previously identified a novel inhibitor of influenza virus in mouse saliva that halts the progression of susceptible viruses from the upper to the lower respiratory tract of mice in vivo and neutralizes viral infectivity in MDCK cells. Here, we investigated the viral target of the salivary inhibitor by using reverse genetics to create hybrid viruses with some surface proteins derived from an inhibitor-sensitive strain and others from an inhibitor-resistant strain. These viruses demonstrated that the origin of the viral neuraminidase (NA), but not the hemagglutinin or matrix protein, was the determinant of susceptibility to the inhibitor. Comparison of the NA sequences of a panel of H3N2 viruses with differing sensitivities to the salivary inhibitor revealed that surface residues 368 to 370 (N2 numbering) outside the active site played a key role in resistance. Resistant viruses contained an EDS motif at this location, and mutation to either EES or KDS, found in highly susceptible strains, significantly increased in vitro susceptibility to the inhibitor and reduced the ability of the virus to progress to the lungs when the viral inoculum was initially confined to the upper respiratory tract. In the presence of saliva, viral strains with a susceptible NA could not be efficiently released from the surfaces of infected MDCK cells and had reduced enzymatic activity based on their ability to cleave substrate in vitro. This work indicates that the mouse has evolved an innate inhibitor similar in function, though not in mechanism, to what humans have created synthetically as an antiviral drug for influenza virus. IMPORTANCE Despite widespread use of experimental pulmonary infection of the laboratory mouse to study influenza virus infection and pathogenesis, to our knowledge, mice do not naturally succumb to influenza. Here, we show that mice produce their own natural form of neuraminidase inhibitor in saliva that stops the virus from reaching the lungs, providing a possible mechanism through which the species may not experience severe influenza virus infection in the wild. We show that the murine salivary inhibitor targets the outer surface of the influenza virus neuraminidase, possibly occluding entry to the enzymatic site rather than binding within the active site like commercially available neuraminidase inhibitors. This knowledge sheds light on how the natural inhibitors of particular species combat infection.


2021 ◽  
Author(s):  
Liang Chen ◽  
Limei Zhu ◽  
Ying Qi

Abstract BackgroundThe Role of respiratory tract commensal bacteria in maintaining the immune homeostasis of the respiratory tract is not well eluciated. We aimed to analyze the effect of respiratory symbiotic bacteria on respiratory immune system and its immune response to exogenous pathogens.MethodsIn this study, SPF C57BL/6 male mice were sensitized by nasal drip of respiratory tract symbiotic bacteria s. aurcus for 6-8 weeks and then used to establish a s. aureus upper respiratory tract symbiosis mouse model. Subsequently, the mice were infected with influenza virus through nasal drip to establish a virus infection model. During the experiment, the immunopathological damage, cytokines and mechanisms related to immune response were analyzed and studied.ResultsThe study found that in the s.aureus upper respiratory tract symbiosis mouse model, s.aurcus sensitization significantly reduced the immune damage in the lungs caused by influenza virus A (IVA) infection, but this protective effect was significantly weakened when alveolar macrophages were cleared. Further studies found that during influenza virus infection, M2 alveolar macrophages (AM) secreted regulatory cytokines to suppress the excessive immune response induced by influenza virus infection. α7nAChR agonist GTS-21 could reduce inflammation in lung tissues, the amount of AM and the expression of inflammatory factors, and the secretion and expression of high-mobility group box 1 (HMGB1) in lung tissues, plasma and bronchoalveolar lavage fluid (BALF). GTS-21 also reduced the lung injury caused by IVA in mice and the levels of M1 type AM bioactive molecules inducible NO synthase (iNOS) and pro-inflammatory factors in AM, and increased the levels of M2 type AM bioactive molecules Arg1 and Ym1. Anti-HMGB 1 antibody reduced the inflammation of lung tissues of mice caused by IVA and inhibited the polarization of AM to M1. Recombinant HMGB1 (rHMGB1) increased the inflammation of lung tissues of mice caused by IVA and promoted the polarization of AM to M1.ConclusionsRespiratory commensal bacteria induced M2 alveolar macrophages with immunomodulatory function to protect the host against illness and death caused by IVA infection.


2017 ◽  
Vol 16 (5) ◽  
pp. 80-86
Author(s):  
E. I. Burtseva ◽  
E. A. Mukasheva ◽  
A. G. Rosatkevich

This paper presents the risk analysis of influenza virus infection in different age groups based on the prevalence and mortality rates. The epidemiological characteristics of the influenza virus circulation during postpandemic period are given. Main aspects of specific and non-specific influenza prevention are discussed. The efficacy of the interferon-based medication Grippferon in the prevention of influenza and acute respiratory viral infections (ARVI) is justified.


2020 ◽  
Vol 43 (3) ◽  
pp. 1-7
Author(s):  
Nattapol Narong ◽  
Siriwat Manajit ◽  
Sirikarn Athipanyasil ◽  
Niracha Athipanyasilp ◽  
Ruengpung Sutthent ◽  
...  

Background: Influenza A (pandemic and seasonal H1/H3) and influenza B viruses were the predominant circulating seasonal influenza strains. Following its massive outbreak in 2009 globally, including Thailand, influenza A (H1N1) pdm09 viruses have replaced the previous seasonal H1 strain and become one of the circulating strains ever since. Both influenza A and B viruses are highly contagious and potentially cause respiratory illness ranging from mild to severe. Objective: To determine the prevalence of types and subtypes of circulating influenza virus strains in Bangkok, Thailand during 2013 - 2017. Methods: The 4385 nasopharyngeal wash specimens were collected from patients presented with influenza-like illness from January 2013 to December 2017 at Siriraj Hospital, Bangkok, Thailand. Influenza virus types and subtypes were determined using real-time RT-PCR technique. Clinical characteristics of patients infected with influenza A viruses and influenza B virus were compared and analyzed. Results: Of 4385 nasopharyngeal wash specimens, the prevalence of influenza virus infection during 2013 - 2017 was 18.22% (n = 799). Of 799 influenza-positive samples, 608 (76.09%) and 191 (23.90%) samples were positive for influenza A and influenza B viruses, respectively. Most patients were presented with fever, cough, and runny nose; however, patients infected with influenza A virus generally had higher severity than those with influenza B virus infection (P < .05). Conclusions: The findings provided the characteristics of influenza virus types and subtypes at Siriraj Hospital, Bangkok, Thailand during 2013 - 2017. Sporadic cases of influenza occurred all year round, but the incidence peaked in March 2014 and August 2017. The outcomes of this study are potentially useful for prevention, treatment, and disease monitoring.  


2021 ◽  
Author(s):  
Nada P. Younis

Several mathematical models with varying degrees of complexity are dedicated to characterizing influenza virus infection kinetics. The majority of existing mathematical models of in-host kinetics are based on ordinary differential equations (ODEs) and do not incorporate viral transport modes. In this work, a spatial model was developed in order to explore, for the first time, the effect of viral transport modes


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