Seasonal influenza epidemics and influenza pandemics caused by influenza A virus (IAV) has resulted in millions of deaths in the world. The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics. Hemagglutinin (HA) of IAV plays a critical role in viral binding, fusion and entry, and contains the major neutralizing epitopes. Therefore, HA is an attractive target for developing anti-IAV drugs and vaccines. Here we have reviewed the recent progress in study of conformational changes of HA during viral fusion process and development of HA-based antiviral therapeutics and vaccines.
Antiviral Agents ; therapeutic use ; Epidemics ; Hemagglutinins ; physiology ; Humans ; Influenza A virus ; immunology ; Influenza Vaccines ; immunology ; Influenza, Human ; immunology ; therapy ; Pandemics

Humans ; Influenza Vaccines ; therapeutic use ; Influenza, Human ; immunology ; prevention & control ; Public Health ; economics ; Vaccination ; economics

The desired effect of vaccination is to elicit protective immune responses against infection with pathogenic agents. An inactivated influenza vaccine is able to induce the neutralizing antibodies directed primarily against two surface antigens, hemagglutinin and neuraminidase. These two antigens undergo frequent antigenic drift and hence necessitate the annual update of a new vaccine strain. Besides the antigenic drift, the unpredictable emergence of the pandemic influenza strain, as seen in the 2009 pandemic H1N1, underscores the development of a new influenza vaccine that elicits broadly protective immunity against the diverse influenza strains. Cold-adapted live attenuated influenza vaccines (CAIVs) are advocated as a more appropriate strategy for cross-protection than inactivated vaccines and extensive studies have been conducted to address the issues in animal models. Here, we briefly describe experimental and clinical evidence for cross-protection by the CAIVs against antigenically distant strains and discuss possible explanations for cross-protective immune responses afforded by CAIVs. Potential barriers to the achievement of a universal influenza vaccine are also discussed, which will provide useful guidelines for future research on designing an ideal influenza vaccine with broad protection without causing pathogenic effects such as autoimmunity or attrition of protective immunity against homologous infection.
Adaptive Immunity ; Antigens, Viral/immunology ; *Cross Protection ; Genome, Viral ; Humans ; Immunity, Innate ; Influenza Vaccines/*immunology/therapeutic use ; Influenza, Human/*prevention & control ; Orthomyxoviridae/genetics/immunology ; Vaccines, Attenuated

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, γδ cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and γδ T cells as well as adaptive CD8 and CD4 T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.
Adaptive Immunity ; Animals ; Cross Protection ; Humans ; Immunity, Innate ; Influenza Vaccines ; therapeutic use ; Influenza, Human ; immunology ; Orthomyxoviridae ; immunology ; Orthomyxoviridae Infections ; immunology ; T-Lymphocytes ; immunology ; Vaccination

Inflammatory bowel disease (IBD) is a long-standing disease that often requires long-term use of immunosuppressive agents including immunomodulators (such as azathioprine, 6-mercaptopurine and methotrexate) and tumor necrosis factor-alpha inhibitors (such as infliximab and adalimumab). Introduction of immunosuppressive therapies, however, involves the risk of host susceptibility to opportunistic infections in this patient population. Therefore, adequate immunization for vaccine-preventable infectious diseases is currently recommended for all patients with IBD and is emerging as an important target for quality improvements in IBD care. However, ongoing issues regarding underuse of immunization, safety and efficacy of vaccines in patients with IBD remain. For quality improvements in IBD care, all physicians should follow the recent immunization guidelines proposed by professional IBD societies. Additionally, there are ongoing needs for intensive educational programs regarding a role of immunization in long-term care of IBD and up-to-date immunization guidelines. Immunization status should be checked at the time of diagnosis of IBD and timely vaccination before initiation of immunosuppressive therapies can be a practical solution for maximizing the efficacy of vaccination at this point. Inactivated vaccines can be used safely irrespective of immunization status of patients, while attenuated vaccines are contraindicated in patients on immunosuppressive therapies. This article reviews an ideal strategy for vaccinating patients with IBD based on the currently recommended immunization guidelines.
Antibodies, Monoclonal/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Inflammatory Bowel Diseases/diagnosis/drug therapy/*immunology ; Influenza Vaccines/immunology ; Influenza, Human/prevention & control ; Pneumonia/prevention & control ; *Vaccination ; Vaccines, Synthetic/immunology

OBJECTIVETo evaluate the safety and immunogenicity of seasonal inactivated influenza vaccine (split virion) and to analyze its cross-reactive antibody responses to H7N9 avian influenza virus.

METHODSAn open-labeled clinical trial was carried out in infants aged 6-35 months, adults aged 18-60 years and the elderly aged >60 years. After vaccinations (one dose for adults and the elderly and two doses for infants), adverse events were observed. Serum samples were obtained before vaccination and 21 days after vaccination from adults and elderly subjects. Three types of antibody against seasonal influenza virus and antibody against H7N9 avian influenza virus were tested using microhemagglutination inhibition (HI) assay. Immunogenicity of the vaccine was evaluated based on the immunogenicity criteria for adults and the elderly, set by the Committee for Medicinal Products for Human Use (CHMP) for the European Medicines Agency.

RESULTSA total of 202 subjects (65 infants, 69 adults and 68 elderly) were enrolled and injected for at least one dose. The overall rate of adverse events was 12.4% (25/202) and most of them were under systemic reaction. No serious adverse event was reported. Pre- and post-vaccination serum samples were collected from 124 subjects (64 adults, 60 elderly). After 21 days of vaccination, the sero-conversion rate, sero-protection rate, and geometric mean titer (GMT) ratio (post-/pre-vaccination) of antibody against seasonal influenza virus were 78.1%-90.6%, 92.2%-100.0% and 7.9-41.0 among adults while 66.7%-83.3%, 86.7%-100.0% and 5.7-20.4 among the elderly, respectively. However, after vaccination, both sero-conversion rate and sero-protection rate of antibody against H7N9 avian influenza virus among adults and the elderly became zero, with GMT ratio between 1.2 and 1.4.

CONCLUSIONThis trial vaccine appeared to have good safety and immunogenicity but inducing no cross-reactive antibody response to H7N9 avian influenza virus.

Adult ; Aged ; Aged, 80 and over ; Antibodies, Viral ; blood ; Antibody Formation ; Child, Preschool ; Cross Reactions ; Hemagglutination Inhibition Tests ; Humans ; Infant ; Influenza A Virus, H7N9 Subtype ; Influenza Vaccines ; immunology ; therapeutic use ; Middle Aged ; Vaccines, Inactivated ; immunology ; therapeutic use ; Young Adult

BACKGROUNDSeasonal influenza epidemic occurs every year in Guangzhou, which can affect all age groups. Young children are the most susceptible targets. Parents can decide whether to vaccinate their children or not based on their own consideration in China. The aim of this study was to identify factors that are important for parental decisions on vaccinating their children against seasonal influenza based on a modified health belief model (HBM).

METHODSA cross-sectional study was conducted in Guangzhou, China. A total of 335 parents who had at least on child aged between 6 months and 3 years were recruited from women and children's hospital in Guangzhou, China. Each eligible subject was invited for a face-to-face interview based on a standardized questionnaire.

RESULTSUptake of seasonal influenza within the preceding 12 months among the target children who aged between 6 months and 36 months was 47.7%. Around 62.4% parents indicated as being "likely/very likely" to take their children for seasonal influenza vaccination in the next 12 months. The hierarchical logistic regression model showed that children's age (odds ratio [OR] =2.59, 95% confidence interval [CI]: 1.44-4.68), social norm (OR = 2.08, 95% CI: 1.06-4.06) and perceived control (OR = 2.96, 95% CI: 1.60-5.50) were significantly and positively associated with children's vaccination uptake within the preceding 12 months; children with a history of taking seasonal influenza vaccine (OR = 2.50, 95% CI: 1.31-4.76), perceived children's health status (OR = 3.36, 95% CI: 1.68-6.74), worry/anxious about their children influenza infection (OR = 2.31, 95% CI: 1.19-4.48) and perceived control (OR = 3.21, 95% CI: 1.65-6.22) were positively association with parental intention to vaccinate their children in the future 12 months. However, anticipated more regret about taking children for the vaccination was associated with less likely to vaccinate children within the preceding 12 months (OR = 0.21, 95% CI: 0.08-0.52).

CONCLUSIONSThe modified HBM provided a good theoretical basic for understanding factors associated with parents' decisions on their children's vaccination against seasonal influenza.

Child, Preschool ; China ; Cross-Sectional Studies ; Female ; Humans ; Infant ; Infant, Newborn ; Influenza Vaccines ; therapeutic use ; Influenza, Human ; immunology ; prevention & control ; Male

INTRODUCTIONOutbreaks of acute respiratory illness occur commonly in long-term care facilities (LTCF), due to the close proximity of residents. Most influenza outbreak reports have been from temperate countries. This study reports an outbreak of influenza B among a highly immunised resident population in a welfare home in tropical Singapore, and discusses vaccine efficacy and the role of acute respiratory illness surveillance for outbreak prevention and control.

MATERIALS AND METHODSDuring the period from 16 to 21 March 2007, outbreak investigations and active case finding were carried out among residents and nursing staff at the welfare home. Interviews and medical notes review were conducted to obtain epidemiological and clinical data. Hospitalised patients were tested for respiratory pathogens. Further genetic studies were also carried out on positive respiratory samples.

RESULTSThe overall clinical attack rate was 9.4% (17/180) in residents and 6.7% (2/30) in staff. All infected residents and staff had received influenza immunisation. Fifteen residents were hospitalised, with 2 developing severe complications. Genetic sequencing revealed that the outbreak strain had an 8.2% amino acid difference from B/Malaysia/2506/2004, the 2006 southern hemisphere influenza vaccine strain, which the residents and staff had earlier received.

CONCLUSIONSA mismatch between the vaccine and circulating influenza virus strains can result in an outbreak in a highly immunised LTCF resident population. Active surveillance for acute respiratory illness in LTCFs could be implemented for rapid detection of antigenic drift. Enhanced infection control and other preventive measures can then be deployed in a timely manner to mitigate the effect of any outbreaks.

Adult ; Aged ; Disease Outbreaks ; prevention & control ; Female ; Humans ; Influenza B virus ; immunology ; Influenza Vaccines ; therapeutic use ; Influenza, Human ; epidemiology ; prevention & control ; virology ; Interviews as Topic ; Male ; Medical Audit ; Middle Aged ; Nursing Homes ; Singapore ; epidemiology ; Social Welfare ; Young Adult

Uveitis was a rare adverse event of vaccination. We met two cases of acute uveitis with exudative retinal detachment following vaccination of H1N1 influenza. Case 1 was a 10-year-old boy who was admitted for bilateral blurred vision at 10 days after vaccination of H1N1 influenza. Vitreous opacity was obvious in both eyes. Broad exudative retinal detachment was observed in the right eye. Case 2 was a 47-year-old female who suffered from an acute high fever at 2 days after the vaccination of H1N1 influenza. Later, she encountered bilateral headache and decreasing vision. In both eyes, mutton fat keratic precipitates, positive Tyndall phenomenon, congestion of optic disc and exudative retinal detachment were observed.
Child ; Female ; Humans ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Influenza Vaccines ; adverse effects ; therapeutic use ; Influenza, Human ; immunology ; prevention & control ; Male ; Middle Aged ; Retinal Detachment ; diagnosis ; etiology ; Uveitis ; diagnosis ; etiology

Novel reassortant H3N2 swine influenza viruses (SwIV) with the matrix gene from the 2009 H1N1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the United States, indicating that H3N2 SwIV might be a potential threat to public health. Since southern China is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring H3N2 subtype SwIV infections, and thus limit the possibility of SwIV infection at agricultural fairs. In this study, a high-growth reassortant virus (GD/PR8) was generated by plasmid-based reverse genetics and tested as a candidate inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice by challenging them with another H3N2 SwIV isolate [A/Swine/Heilongjiang/1/05 (H3N2) (HLJ/05)]. Prime and booster inoculation with GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting antibodies and IgG antibodies. Complete protection of mice against H3N2 SwIV was observed, with significantly reduced lung lesion and viral loads in vaccine-inoculated mice relative to mock-vaccinated controls. These results suggest that the GD/PR8 vaccine may serve as a promising candidate for rapid intervention of H3N2 SwIV outbreaks in China.
Animals ; Female ; Influenza A Virus, H3N2 Subtype/*genetics/immunology ; Influenza Vaccines/genetics/immunology/*therapeutic use ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections/immunology/*prevention & control/virology ; Reassortant Viruses/genetics/immunology ; Reverse Genetics/methods/*veterinary ; Swine ; Swine Diseases/immunology/*prevention & control/virology ; Vaccines, Inactivated ; Virus Replication