A Combination of Deworming and Prime-Boost Vaccination Regimen Restores Efficacy of Vaccination Against Influenza in Helminth-Infected Mice

Helminths still infect a quarter of the human population. They manage to establish chronic infections by downmodulating the immune system of their hosts. Consequently, the immune response of helminth-infected individuals to vaccinations may be impaired as well. Here we study the impact of helminth-induced immunomodulation on vaccination efficacy in the mouse system. We have previously shown that an underlying Litomosoides sigmodontis infection reduced the antibody (Ab) response to anti-influenza vaccination in the context of a systemic expansion of type 1 regulatory T cells (Tr1). Most important, vaccine-induced protection from a challenge infection with the 2009 pandemic H1N1 influenza A virus (2009 pH1N1) was impaired in vaccinated, L. sigmodontis-infected mice. Here, we aim at the restoration of vaccination efficacy by drug-induced deworming. Treatment of mice with Flubendazole (FBZ) resulted in elimination of viable L. sigmodontis parasites in the thoracic cavity after two weeks. Simultaneous FBZ-treatment and vaccination did not restore Ab responses or protection in L. sigmodontis-infected mice. Likewise, FBZ-treatment two weeks prior to vaccination did not significantly elevate the influenza-specific Ig response and did not protect mice from a challenge infection with 2009 pH1N1. Analysis of the regulatory T cell compartment revealed that L. sigmodontis-infected and FBZ-treated mice still displayed expanded Tr1 cell populations that may contribute to the sustained suppression of vaccination responses in successfully dewormed mice. To outcompete this sustained immunomodulation in formerly helminth-infected mice, we finally combined the drug-induced deworming with an improved vaccination regimen. Two injections with the non-adjuvanted anti-influenza vaccine Begripal conferred 60% protection while MF59-adjuvanted Fluad conferred 100% protection from a 2009 pH1N1 infection in FBZ-treated, formerly L. sigmodontis-infected mice. Of note, applying this improved prime-boost regimen did not restore protection in untreated L. sigmodontis-infected mice. In summary our findings highlight the risk of failed vaccinations due to helminth infection.

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Could Environment Affect the Mutation of H1N1 Influenza Virus?

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17093092 ◽

2020 ◽

Vol 17 (9) ◽

pp. 3092

Author(s):

Dong Jiang ◽

Qian Wang ◽

Zhihua Bai ◽

Heyuan Qi ◽

Juncai Ma ◽

...

Keyword(s):

Influenza Virus ◽

Environmental Factors ◽

Social Development ◽

Influenza A ◽

H1n1 Influenza ◽

Influenza A Viruses ◽

Nighttime Light ◽

Complex Relationships ◽

The Impact ◽

The Relationship

H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000–2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors.

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Influenza and Community-acquired Pneumonia Interactions: The Impact of Order and Time of Infection on Population Patterns

American Journal of Epidemiology ◽

10.1093/aje/kwr402 ◽

2012 ◽

Vol 175 (5) ◽

pp. 363-367 ◽

Cited By ~ 11

Author(s):

Brian M. Davis ◽

Allison E. Aiello ◽

Suzanne Dawid ◽

Pejman Rohani ◽

Sourya Shrestha ◽

...

Keyword(s):

Influenza A ◽

Animal Studies ◽

Severe Disease ◽

Severity Of Illness ◽

Population Level ◽

Community Acquired Pneumonia ◽

Swine Flu ◽

1918 Influenza ◽

The Impact

AbstractDiscoveries made during the 1918 influenza A pandemic and reports of severe disease associated with coinfection during the 2009 hemagglutinin type 1 and neuraminidase type 1 (commonly known as H1N1 or swine flu) pandemic have renewed interest in the role of coinfection in disease pathogenesis. The authors assessed how various timings of coinfection with influenza virus and pneumonia-causing bacteria could affect the severity of illness at multiple levels of interaction, including the biologic and population levels. Animal studies most strongly support a single pathway of coinfection with influenza inoculation occurring approximately 7 days before inoculation with Streptococcus pneumoniae, but less-examined pathways of infection also may be important for human disease. The authors discussed the implications of each pathway for disease prevention and what they would expect to see at the population level if there were sufficient data available. Lastly, the authors identified crucial gaps in the study of timing of coinfection and proposed related research questions.

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The impact of H1N1 influenza A virus pandemic on the emergency medical service in Kobe

The American Journal of Emergency Medicine ◽

10.1016/j.ajem.2009.10.013 ◽

2010 ◽

Vol 28 (2) ◽

pp. 248-251 ◽

Cited By ~ 4

Author(s):

Masaharu Tsubokura ◽

Haruka Nakada ◽

Tomoko Matsumura ◽

Yuko Kodama ◽

Masahiro Kami

Keyword(s):

Emergency Medical Service ◽

Influenza A Virus ◽

Influenza A ◽

Medical Service ◽

H1n1 Influenza ◽

Emergency Medical ◽

The Impact

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Assessing the impact of public health interventions on the transmission of pandemic H1N1 influenza a virus aboard a Peruvian navy ship

Influenza and Other Respiratory Viruses ◽

10.1111/irv.12240 ◽

2014 ◽

Vol 8 (3) ◽

pp. 353-359 ◽

Cited By ~ 9

Author(s):

Delphis M. Vera ◽

Ricardo A. Hora ◽

Anarina Murillo ◽

Juan F. Wong ◽

Armando J. Torre ◽

...

Keyword(s):

Public Health ◽

Influenza A Virus ◽

Influenza A ◽

H1n1 Influenza ◽

Health Interventions ◽

Pandemic H1n1 ◽

Public Health Interventions ◽

Pandemic H1n1 Influenza ◽

The Impact

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Vaccination against swine flu caused narcolepsy in several european countries

Health Risk Analysis ◽

10.21668/health.risk/2020.3.22.eng ◽

2020 ◽

pp. 182-187

Author(s):

I. Boström ◽

◽

O. Lindberger ◽

M. Partinen ◽

A.M. Landtblom ◽

...

Keyword(s):

Influenza A ◽

Strong Association ◽

Diagnostic Delay ◽

Sleep Onset ◽

H1n1 Influenza ◽

European Countries ◽

Swine Flu ◽

Increased Risk ◽

2009 H1n1

Narcolepsy is a rare sleeping disorder that gives sleep onset rapid eye movement periods and excessive daytime sleepiness. It is divided into two subgroups, narcolepsy type 1 where there also is orexin deficiency and cataplexy and narcolepsy type 2 that lack these features. Narcolepsy type 1 is assumed to be an autoimmune disease with destruction of orexinproducing cells. The pathology behind is unclear. There is a strong association to a class II HLA allele, HLADQB1*06:02 and the H1N1-virus and streptococcal infections has also been associated with narcolepsy. The severity of narcolepsy differs between patients from those who can manage their disease without medication to those who has a severe impact on their everyday life. There is a diagnostic delay between the onset of symptoms and time for diagnosis that in some cases can be more than a decade. The global mean prevalence is 30 per 100 000 inhabitants. The incidence in children in northern Europe has risen since 2010. An early study of the 2009 H1N1 influenza A pandemic indicated a high mortality and prompted efforts to rapidly come up with a vaccine. One of these was Pandemrix that was the most widely used in Europe and 61 % of the inhabitants in Sweden was vaccinated. Studies have shown an increased incidence of narcolepsy type 1 in European countries that had used Pandemrix, but no increased risk was seen in countries that had used other vaccines than Pandemrix.

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Vaccination against swine flu caused narcolepsy in several european countries

Health Risk Analysis ◽

10.21668/health.risk/2020.3.22 ◽

2020 ◽

pp. 182-187

Author(s):

I. Boström ◽

◽

O. Lindberger ◽

M. Partinen ◽

A.M. Landtblom ◽

...

Keyword(s):

Influenza A ◽

Strong Association ◽

Diagnostic Delay ◽

Sleep Onset ◽

H1n1 Influenza ◽

European Countries ◽

Swine Flu ◽

Increased Risk ◽

2009 H1n1

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The impact of H1N1 influenza A virus pandemic on the blood donations in Hyogo Prefecture, Japan

Transfusion ◽

10.1111/j.1537-2995.2010.02641.x ◽

2010 ◽

Vol 50 (8) ◽

pp. 1803-1805 ◽

Cited By ~ 3

Author(s):

Masaharu Tsubokura ◽

Haruka Nakada ◽

Tomoko Matsumura ◽

Yuko Kodama ◽

Hiroto Narimatsu ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

H1n1 Influenza ◽

Blood Donations ◽

Hyogo Prefecture ◽

The Impact

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Drug Induced Changes in Cell Organelles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100299 ◽

1968 ◽

Vol 26 ◽

pp. 110-111

Author(s):

Sarah A. Luse

Keyword(s):

Clinical Medicine ◽

Cell Organelles ◽

Riboflavin Deficiency ◽

Drug Induced ◽

New Era ◽

Health And Disease ◽

In The Beginning ◽

Cellular Pathology ◽

Induced Changes ◽

The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

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