Strategies to enhance intranasal flu vaccine effectiveness still pose a risk of viral mutation back to the pandemic strain.

PMID: 

PLoS One. 2011 ;6(5):e19863. Epub 2011 May 20. PMID: 21625486

Abstract Title: 

Intranasal immunization with recombinant HA and mast cell activator C48/80 elicits protective immunity against 2009 pandemic H1N1 influenza in mice.

Abstract: 

BACKGROUND: Pandemic influenza represents a major threat to global health. Vaccination is the most economic and effective strategy to control influenza pandemic. Conventional vaccine approach, despite being effective, has a number of major deficiencies including limited range of protection, total dependence on embryonated eggs for production, and time consuming for vaccine production. There is an urgent need to develop novel vaccine strategies to overcome these deficiencies.METHODOLOGY/PRINCIPAL FINDINGS: The major objective of this work was to develop a novel vaccine strategy combining recombinant haemagglutinin (HA) protein and a master cell (MC) activator C48/80 for intranasal immunization. We demonstrated in BALB/c mice that MC activator C48/80 had strong adjuvant activity when co-administered with recombinant HA protein intranasally. Vaccination with C48/80 significantly increased the serum IgG and mucosal surface IgA antibody responses against HA protein. Such increases correlated with stronger and durable neutralizing antibody activities, offering protection to vaccinated animals from disease progression after challenge with lethal dose of A/California/04/2009 live virus. Furthermore, protected animals demonstrated significant reduction in lung virus titers, minimal structural alteration in lung tissues as well as higher and balanced production of Th1 and Th2 cytokines in the stimulated splenocytes when compared to those without C48/80.CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that the novel vaccine approach of combining recombinant HA and mucosal adjuvant C48/80 is safe and effective in eliciting protective immunity in mice. Future studies on the mechanism of action of C48/80 and potential combination with other vaccine strategies such as prime and boost approach may help to induce even more potent and broad immune responses against viruses from various clades.

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The live attentuated influenza vaccine can alter bacterial transmigration towards the middle ear and increase the risk of otitis media. This risk was not clinically investigated before the implementation of the vaccine.

PMID: 

J Infect Dis. 2015 Jul 15 ;212(2):195-201. Epub 2014 Dec 11. PMID: 25505300

Abstract Title: 

Live attenuated influenza virus increases pneumococcal translocation and persistence within the middle ear.

Abstract: 

BACKGROUND: Infection with influenza A virus (IAV) increases susceptibility to respiratory bacterial infections, resulting in increased bacterial carriage and complications such acute otitis media, pneumonia, bacteremia, and meningitis. Recently, vaccination with live attenuated influenza virus (LAIV) was reported to enhance subclinical bacterial colonization within the nasopharynx, similar to IAV. Although LAIV does not predispose to bacterial pneumonia, whether it may alter bacterial transmigration toward the middle ear, where it could have clinically relevant implications, has not been investigated.METHODS: BALB/c mice received LAIV or phosphate-buffered saline 1 or 7 days before or during pneumococcal colonization with either of 2 clinical isolates, 19F or 7F. Middle ear bacterial titers were monitored daily via in vivo imaging.RESULTS: LAIV increased bacterial transmigration to and persistence within the middle ear. When colonization followed LAIV inoculation, a minimum LAIV incubation period of 4 days was required before bacterial transmigration commenced.CONCLUSIONS: While LAIV vaccination is safe and effective at reducing IAV and coinfection with influenza virus and bacteria, LAIV may increase bacterial transmigration to the middle ear and could thus increase the risk of clinically relevant acute otitis media. These data warrant further investigations into interactions between live attenuated viruses and naturally colonizing bacterial pathogens.

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Guillain-Barre Syndrome may occur as a result of molecular mimicry.

PMID: 

Neurol Neurochir Pol. 2005 May-Jun;39(3):230-6. PMID: 15981163

Abstract Title: 

[Guillain-Barré Syndrome and its association with infectious factors].

Abstract: 

Guillain-Barré Syndrome (GBS) is an acute polyneuropathy often triggered by inflammatory and probably autoimmune mechanisms. Development of GBS is in 2/3 of cases preceded by acute infection, typically with gastrointestinal or respiratory symptoms. Infectious agents related to GBS include cytomegalovirus, Epstein-Barr virus, Campylobacter jejuni, Mycoplasma pneumoniae and Haemophilus influenzae. Molecular mimicry seems to be responsible for GBS development after infection, through the synthesis of autoantibodies against myelin gangliosides. Autoimmune reactions develop only in a small fraction of all exposed individuals, depending on still unresolved factors. Different infections lead to forms of GBS differing in spectrum of autoantibodies and in frequency with which different clinical symptoms appear. This may be of some significance for early prognosis and in future possibly for choosing therapeutic options. An increased risk of GBS may be also related to vaccination, but with presently used vaccines this increase remains below one case of GBS per one million doses.

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A case report of anaphylaxis following influenza vaccination, attributed to the gelatin and ovalbumin in the vaccine.

PMID: 

Int Arch Allergy Immunol. 2008 ;146(1):85-8. Epub 2007 Dec 14. PMID: 18087166

Abstract Title: 

Anaphylaxis from the influenza virus vaccine.

Abstract: 

BACKGROUND: Allergic reactions to the influenza vaccine are uncommon and usually associated with sensitivity to egg or gelatin. The aim of this study was to report the case of anaphylaxis to the influenza vaccine.METHODS: Allergy percutaneous skin testing, serum specific IgE testing and IgE immunoblotting were performed to the influenza vaccine, egg, and gelatin.RESULTS: Percutaneous skin testing to the influenza vaccine and gelatin were positive and egg (white, whole, and yolk) was negative. Immunocap serum-specific IgE testing to egg (white, whole, and yolk) and gelatin were negative (

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Guillain-Barre syndrome can be induced by vaccination or infection.

PMID: 

Clin Rev Allergy Immunol. 2012 Apr ;42(2):121-30. PMID: 20890797

Abstract Title: 

Guillain-Barré syndrome–a classical autoimmune disease triggered by infection or vaccination.

Abstract: 

Guillain-Barré syndrome (GBS) is a rare autoimmune disorder, the incidence of which is estimated to be 0.6-4/100,000 person/year worldwide. Often, GBS occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal microbial infection. The disorder is sub-acute developing overthe course of hours or days up to 3 to 4 weeks. About a third of all cases of Guillain-Barré syndrome are preceded by Campylobacter jejuni infection. C. jejuni strains isolated from GBS patients have a lipooligosaccharide (LOS) with a GM1-like structure. Molecular mimicry between LOS and the peripheral nerves as a cause of GBS was demonstrated in animal models of human GBS. Following the"swine flu"virus vaccine program in the USA in 1976, an increase in incidence of GBS was observed and the calculated relative risk was 6.2. Later studies have found that influenza vaccines contained structures that can induce anti-GM1 (ganglioside) antibodies after inoculation into mice. More recent information has suggested that the occurrence of GBS after currently used influenza and other vaccines is rare. GBS involves genetic and environmental factors, may be triggered by infections or vaccinations, and predisposition can be predicted by analyzing some of these factors.

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Influenza vaccines contain measurable quantities of residual egg white protein.

PMID: 

Pediatr Clin North Am. 2011 Apr ;58(2):427-43, xi. PMID: 21453811

Abstract Title: 

Current understanding of egg allergy.

Abstract: 

Egg is one of the most important allergens in childhood feeding, and egg allergy can pose quality-of-life concerns. A clear clinical history and the detection of egg white-specific immunoglobulin E (IgE) will confirm the diagnosis of IgE-mediated reactions. Non-IgE-mediated symptoms, such as those of eosinophilic diseases of the gut, might also be observed. Egg avoidance and education regarding the treatment of allergic reactions are the cornerstones of management of egg allergy. This article discusses epidemiology, risk factors, diagnosis, treatment, and natural history of egg allergy.

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The respiratory syncytial virus live vaccine is ineffective in infants younger than 4 months.

PMID: 

Vaccine. 2014 Aug 20 ;32(37):4726-9. Epub 2014 Jul 6. PMID: 25005882

Abstract Title: 

The association between age and the development of respiratory syncytial virus neutralising antibody responses following natural infection in infants.

Abstract: 

To determine the age at which infants mount significant neutralising antibody responses to both natural RSV infection and live vaccines that mimic natural infection, RSV-specific neutralising antibodies in the acute and convalescent phase sera of infants with RSV infection were assayed. Age-specific incidence estimates for hospitalisation with severe RSV disease were determined and compared to age-specific neutralising antibody response patterns. Disease incidence peaked at between 2 and 3.9 months of life. Following natural infection, relative to the mean acute phase antibody titre, the mean convalescent titre was lower in the 0-1.9 month age class, no different in the 2-3.9 month age class and greater in all age classes greater than 4 months. These data suggest effective vaccination with live vaccines that mimic natural infection may not be achieved before the age of 4 months. Maternal vaccination may be an alternative to direct infant vaccination in order to protect very young babies.

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A case report of aluminum granuloma after DTaP-IPV vaccination.

PMID: 

Pediatr Dermatol. 2019 Jan ;36(1):e17-e19. Epub 2018 Nov 28. PMID: 30488642

Abstract Title: 

Aluminum granuloma in a child secondary to DTaP-IPV vaccination: A case report.

Abstract: 

Reports detailing the acute formation of aluminum granulomas, which can cause persistent, intensely pruritic nodules secondary to the administration of aluminum-containing vaccines, are infrequently described in medical literature. To our knowledge, this is the first report describing the development of an aluminum granuloma causing a persistent, pruritic nodule at the injection site following the administration of the DTaP-IPV vaccine. We present the case of a 6-year-old girl who developed a severely pruritic subcutaneous nodule on her anterior right thigh at the injection site three weeks after the administration of the aluminum-containing DTaP-IPV (Kinrix) vaccine. The nodule was eventually excised 14 months after its initial appearance, after which her symptoms resolved. Histologic inspection demonstrated a dense, deep dermal and subcutaneous nodular mixed infiltrate of lymphocytes, histiocytes, and eosinophils, with germinal center formation. The bluish, amphophilic granular cytoplasm found in most of the histiocytes is a characteristic feature of"aluminum granulomas."This adverse reaction should be considered in any patient presenting with similar findings in the weeks following a DTaP-IPV vaccination or other aluminum-containing vaccines. Furthermore, the self-limiting tendency of these nodules should not preclude affected patients from any future vaccinations, though vaccines without aluminum should be preferentially selected when possible.

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A case report of acute cerebellar ataxia after hepatitis B vaccination.

PMID: 

Acta Neurol Scand. 1994 Jun ;89(6):462-3. PMID: 7976236

Abstract Title: 

Acute cerebellar ataxia after immunisation with recombinant hepatitis B vaccine.

Abstract: 

We report one woman with acute cerebellar ataxia (ACA), a well-defined clinical syndrome, which occurred 10 days after the second vaccination with recombinant hepatitis B vaccine. The patient had no previous symptoms or signs of neurological disease and there was no evidence of neurologic disease in the family history. Within nine months the symptoms remitted completely according to other reports of ACA. As there was a close temporal connection and no noticeable other cause we assume a causal link between the vaccination and the disease. As far as we known this is the first case of ACA after hepatitis B vaccination.

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