High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza

To, Kelvin Kai-Wang; Zhang, Anna Jinxia; Hung, Ivan F. N.; Xu, Ting; Ip, Whitney C.T.; Wong, Rebecca T. Y.; Ng, Joseph C. K.; Chan, Jasper Fuk‐Woo; Chan, Kwok‐Hung; Yuen, Kwok‐Yung

doi:10.1128/cvi.00081-12

Cited by 81 publications

(84 citation statements)

References 51 publications

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“…High titers of serum Abs of low avidity for H1-2009 antigen in severely ill individuals have often been associated with mortality (12). To et al, however, have proposed that nonneutralizing Abs with high avidity might also be associated with severe illness during influenza A(H1N1)pdm09 infection (13,14). Individuals who survive are thus those who mounted an immune response.…”

Section: Introductionmentioning

confidence: 99%

Characterization of pandemic influenza immune memory signature after vaccination or infection

Bonduelle¹,

Carrat²,

Luyt³

et al. 2014

J. Clin. Invest.

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The magnitude, quality, and maintenance of immunological memory after infection or vaccination must be considered for future design of effective influenza vaccines. In 2009, the influenza pandemic produced disease that ranged from mild to severe, even fatal, illness in infected healthy adults and led to vaccination of a portion of the population with the adjuvanted, inactivated influenza A(H1N1)pdm09 vaccine. Here, we have proposed a multiparameter quantitative and qualitative approach to comparing adaptive immune memory to influenza 1 year after mild or severe infection or vaccination. One year after antigen encounter, severely ill subjects maintained high levels of humoral and polyfunctional effector/memory CD4 + T cells responses, while mildly ill and vaccinated subjects retained strong cellular immunity, as indicated by high levels of mucosal homing and degranulation markers on IFN-γ + antigen-specific T cells. A principal component analysis distinguished 3 distinct clusters of individuals. The first group comprised vaccinated and mildly ill subjects, while clusters 2 and 3 included mainly infected individuals. Each cluster had immune memory profiles that differed in magnitude and quality. These data provide evidence that there are substantial similarities between the antiinfluenza response that mildly ill and vaccinated individuals develop and that this immune memory signature is different from that seen in severely ill individuals.

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Section: Introductionmentioning

confidence: 99%

Characterization of pandemic influenza immune memory signature after vaccination or infection

Bonduelle¹,

Carrat²,

Luyt³

et al. 2014

J. Clin. Invest.

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“…Rapid induction of a neutralizing antibody response by influenza vaccine is essential in the early control of influenza, especially during a novel pandemic or avian influenza outbreak in an immunologically naive population (38). The influenza vaccines currently available for human use require 14 to 21 days to achieve adequate levels of neutralizing antibody, even if an adjuvant is added to the vaccine (5,42,43).…”

Section: Discussionmentioning

confidence: 99%

“…Vaccine antigen was used to coat 96-well immunoplates (Nunc-Immuno Modules; Nunc A/S, Roskilde, Denmark) at 100 l per well containing 2 g of HA/ml in 0.05 M NaHCO 3 (pH 9.6) as described previously (38). The plate was incubated at 4°C overnight and then blocked with 1% normal goat serum at 37°C for 1 h. One hundred microliters of diluted serum was added, and the mixture was incubated at 37°C for 1 h. The plate was washed six times with PBS before 100 l of horseradish peroxidase-conjugated secondary antibodies (Life Technology, Carlsbad, CA) was added and the mixture was incubated for 1 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…n ϭ 6 per group. RDE-treated serum samples (38,39). The HAI test was performed by incubating 25 l of serially 2-fold-diluted (starting at 1:10) serum with 25 l of 4 hemagglutination units of mouse-adapted A(H1N1)pdm09 virus at room temperature for 1 h. The plates were read after 40 min of incubation with 50 l of 0.5% turkey red blood cells (Lampire Biological Laboratories, Pipersville, PA).…”

Section: Methodsmentioning

confidence: 99%

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Toll-Like Receptor 7 Agonist Imiquimod in Combination with Influenza Vaccine Expedites and Augments Humoral Immune Responses against Influenza A(H1N1)pdm09 Virus Infection in BALB/c Mice

Zhang

et al. 2014

Clin Vaccine Immunol

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Toll-like receptors (TLRs) of the innate immune system are known targets for enhancing vaccine efficacy. We investigated whether imiquimod, a synthetic TLR7 agonist, can expedite the immune response against influenza virus infection when combined with influenza vaccine. BALB/c mice were immunized intraperitoneally with monovalent A(H1N1)pdm09 vaccine combined with imiquimod (VCI) prior to intranasal inoculation with a lethal dose of mouse-adapted A(H1N1)pdm09 virus. For mice immunized 3 days before infection, the survival rates were significantly higher in the VCI group (60%, mean survival time[MST], 11 days) than in the vaccine-alone (30%; MST, 8.8 days), imiquimod-alone (5%; MST, 8.4 days), and phosphate-buffered saline (PBS) (0%; MST, 6.2 days) groups (P < 0.01). In the VCI group, 45 and 35% of the mice survived even when they were infected 2 days or 1 day after immunization. Virus-specific serum IgM, IgG, and neutralizing antibodies appeared earlier with higher geometric mean titers in the VCI group than in the control groups. The pulmonary viral load was significantly lower at all time points postinfection in the VCI, vaccine-alone, and imiquimod-alone groups than in the PBS control group (P < 0.05). The protection induced by VCI was specific for A(H1N1)pdm09 virus but not for A(H5N1) virus. Since imiquimod combined with RNase-treated vaccine is as protective as imiquimod combined with untreated vaccine, mechanisms other than TLR7 may operate in expediting and augmenting immune protection. Moreover, increased gamma interferon mRNA expression and IgG isotype switching, which are markers of the Th1 response induced by imiquimod, were not apparent in our mouse model. The mechanisms of imiquimod-induced immune protection deserve further study.

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“…Annual vaccination with injectable influenza vaccines may interfere with the development of broad immunity against influenza that could otherwise be induced by natural infection [11]. Vaccination-related effects sometimes exacerbate viral infections (e.g., respiratory syncytial virus; dengue virus; measles virus; influenza virus) [12][13][14]. The consequence of a vaccination-induced polarized T-cell memory profile on clinical outcomes is largely a terra incognita [15,16].…”

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confidence: 99%

Noninvasive vaccination as a casus belli to redeem vaccine value in the face of anti-vaccine movements

Tang¹

2017

Integr Mol Med

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Formidable anti-vaccine movements have been growing as a menace to disrupt beneficial vaccine programs. Although the vaccination-associated adverse effects commonly perceived by vaccine resisters usually represent over-reactions to rare manifestations, converging evidence shows that vaccination-associated health threats could be pervasive when systemic inflammation is considered as a side effect that oozes over time. An anti-vaccine movement thus may not be so unfounded even though the myriad cascades triggered by systemic inflammation have not been brought to a clear focus during any anti-vaccine campaign. Since both pro-and antivaccine groups are acting on the same primal impulse -"keep people healthy," reconciliation between the two warring factions should be achievable on a palatable trend that fosters the development of noninvasive vaccines which tend to induce local and transient inflammation along the interface with diminished potential to percolate through internal organs. Anti-vaccine movements fueled by vaccines' incertitudeVaccination is widely heralded as a medical paradigm credited with mitigation of many vaccination-preventable diseases through massimmunization programs. However, its success has also precipitated an active opposition. The genesis of the anti-vaccine movement surge could be traced back to the anti-vaccine sentiment catalyzed by the Britain's Compulsory Vaccination Act of 1853, which mandated the vaccination of all infants [1]. The controversial pertussis and hepatitis B virus (HBV) vaccines in conjunction with the apocryphal link between vaccination and autism not only re-catalyzed a groundswell of antivaccine activism but catapulted it into a phase of erudite opposition [2].Anti-vaccine groups are formed mostly by affluent "knowledge seekers" who claim the right to make "informed choices" about vaccination [2][3][4]. Today's vaccines largely represent a double-edged sword to vaccine resisters even though they are agnostic about what causes vaccines' side effects. Regardless of their creeds, the incipient anti-vaccine movements have been implicated in low vaccine coverages in conjunction with hazardous outbreaks of preventable diseases [5].The grand success of vaccination programs is undeniable, and no anti-vaccine groups in the modern era have advocated a divorce by forbidding vaccines altogether in the medical arsenal. The schism between vaccine supporters and resisters can be attributed to the scope of restricted use of vaccines. Vaccine supporters' zeitgeist is based on the belief that vaccines' risks are minuscule with their core health benefits in vanquishing diseases far eclipse their risks, whereas vaccine resisters fear the brunt of vaccination due to vaccines' incertitude and their arcane mechanisms of action. Overall, the bifurcated stances are not as mutually exclusive from an ethical perspective.Vaccine supporters often impugn vaccine resisters for avoiding vaccination against communicable diseases on the premise that individuals opting out of immunization may j...

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High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza

Cited by 81 publications

References 51 publications

Characterization of pandemic influenza immune memory signature after vaccination or infection

Characterization of pandemic influenza immune memory signature after vaccination or infection

Toll-Like Receptor 7 Agonist Imiquimod in Combination with Influenza Vaccine Expedites and Augments Humoral Immune Responses against Influenza A(H1N1)pdm09 Virus Infection in BALB/c Mice

Noninvasive vaccination as a casus belli to redeem vaccine value in the face of anti-vaccine movements

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