A pan-influenza antibody inhibiting neuraminidase via receptor mimicry.

Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift1 and suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses.

What to Do in the Next Pandemic Outbreak: Natural Herd Immunity Versus Lockdown (Lessons Learned from COVID-19).

The purpose of this article is to analyse non-pharmaceutical approaches to control pandemics. Currently vaccines are our best hope to control the COVID-19 pandemic, but before the appearance of the first vaccines the available possibilities were much more limited. While most people worldwide were confined to their homes to slow the spread of the new coronavirus, some countries (most notably the United Kingdom) advocated infecting the majority of the community, aiming to achieve what has been called "herd immunity". This article focuses on two non-therapeutic strategies for dealing with deadly viruses and points out their respective problems: natural herd immunity and quarantines/lockdowns. It analyses these strategies from three perspectives: legal, ethical and social. The article concludes that in the absence of therapeutic alternatives (vaccines), short-term lockdowns are necessary, but long-term lockdowns are legally, ethically, socially and financially impossible to sustain.

Reassessment of the risk of narcolepsy in children in England 8 years after receipt of the AS03-adjuvanted H1N1 pandemic vaccine: A case-coverage study.

BACKGROUND: Early studies of narcolepsy after AS03-adjuvanted pandemic A/H1N12009 vaccine (Pandemrix) could not define the duration of elevated risk post-vaccination nor the risk in children aged under 5 years who may not present until much older. METHODS/FINDINGS: Clinical information and sleep test results, extracted from hospital notes at 3 large pediatric sleep centers in England between September 2017 and June 2018 for narcolepsy cases aged 4-19 years with symptom onset since January 2009, were reviewed by an expert panel to confirm the diagnosis. Vaccination histories were independently obtained from general practitioners (GPs). The odds of vaccination in narcolepsy cases compared with the age-matched English population was calculated after adjustment for clinical conditions that were indications for vaccination. GP questionnaires were returned for 242 of the 244 children with confirmed narcolepsy. Of these 5 were under 5 years, 118 were 5-11 years, and 119 were 12-19 years old at diagnosis; 39 were vaccinated with Pandemrix before onset. The odds ratio (OR) for onset at any time after vaccination was 1.94 (95% confidence interval [CI] 1.30-2.89), The elevated risk period was restricted to onsets within 12 months of vaccination (OR 6.65 [3.44-12.85]) and was highest within the first 6 months. After one year, ORs were not significantly different from 1 up to 8 years after vaccination. The ORs were similar in under five-year-olds and older ages. The estimated attributable risk was 1 in 34,500 doses. Our study is limited by including cases from only 3 sleep centers, who may differ from cases diagnosed in nonparticipating centers, and by imprecision in defining the centers' catchment population. The potential for biased recall of onset shortly after vaccination in cases aware of the association cannot be excluded. CONCLUSIONS: In this study, we found that vaccine-attributable cases have onset of narcolepsy within 12 months of Pandemrix vaccination. The attributable risk is higher than previously estimated in England because of identification of vaccine-attributable cases with late diagnoses. Absence of a compensatory drop in risk 1-8 years after vaccination suggests that Pandemrix does not trigger onsets in those in whom narcolepsy would have occurred later.

Informe diário de evidências COVID-19: busca realizada em 29 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 29, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 3 protocolos.

Informe diário de evidências COVID-19: busca realizada em 30 de junho de 2020 / COVID-19 daily evidence report: search conducted on June 30, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 31 protocolos.

[Adjuvants of influenza vaccines: new possibilities of using sulphated polysaccharides from marine brown algae.]

The review article presents the characteristics of the main adjuvant groups (mineral salts of aluminum, synthetic squalenebased adjuvants - MF59 and AS03, CpG-oligodeoxynucleotides, virosomes, polyoxidonium, sovidone) included in the licensed influenza vaccine. The main mechanisms of adjuvant action, advantages and disadvantages of these adjuvants are shown. The vaccines adjuvants in the phase of experimental studies and clinical trials (ISCOMs, Advax™, chitosan) are described too. Particular attention is paid to sulfated polysaccharides (fucoidans) from marine brown algae as vaccine adjuvants. Numerous results of their application in compositions of experimental vaccines are presented. The prospects of sulfated polysaccharides using in the design of influenza vaccines are estimated. These prospects are determined by high biocompatibility, low toxicity and good tolerance of the human body to fucoidans, as well as mechanisms of their adjuvant activity. Sulfated polysaccharides are agonists of toll-like receptors of innate immunity cells and powerful inducers of the cellular and humoral immune response, which is important for the development of influenza vaccines. The review is based on the information presented in the bibliographic and abstract databases of scientific publications, search engines and publishers: RSCI, Web of Science, Scopus, MEDLINE, Google Scholar, PubMed, Springer Nature, Elsevier and others.

Preventive care among primary care patients living with spinal cord injury.

Objective: Context/Objective: Family physicians may lack the knowledge or resources to adequately support patients with spinal cord injury (SCI). Our objectives were to determine patterns of preventive care for patients with SCI in a primary care setting (i.e. cancer screening, influenza vaccinations, general physicals, bone mineral density tests), and determine physicians' level of comfort with providing primary care to patients with SCI.Design: i) Retrospective chart review, ii) Survey of physicians in the family practice.Setting: Six primary care practice sites in Ontario, Canada.Participants: All adult rostered patients of the family practice with SCI; All family physicians in the six sites.Outcome Measures: Proportion of patients up-to-date on cancer screening, proportion of patients with influenza vaccinations, general physicals, bone mineral density tests; physicians' level of comfort with providing care to patients with SCI.Results: Sixty patients were included in analyses. Rates of cancer screening were generally poor. The highest uptake was seen for cervical cancer screening, where 50% of eligible women were up-to-date on Pap tests. Only 36.7% of patients were up-to-date on colorectal cancer screening. Only 14 (23.3%) patients had a documented general physical exam in their electronic record. There was a recorded flu vaccination for 55% of patients, and of those, there was a median of 19 months since last vaccination. Fifteen physicians (21.4%) responded to the survey. Ten physicians reported at least one patient with SCI, with the maximum being 20 patients. Comfort level in managing SCI-relevant conditions varied and was lowest for spasticity, respiratory issues and autonomic dysreflexia, where only 27.3% of respondents had some level of comfort.Conclusion There are many opportunities to improve the preventive care of patients living with SCI.

[Prevention of Infections of the Upper Respiratory Tract]. / Prävention von Infekten der oberen Atemwege.

Because of its high prevalence acute respiratory diseases have a significant impact on the population. The focus of this review was the current state of knowledge for the prophylactic efficacy of: zinc, vitamin C, Echinacea preparations, garlic and carrying out physical measures. Furthermore, the benefits of pneumococcal and influenza vaccine were elicited. In the synopsis, the physical measures proved to be the most effective, cost-effective method to prevent infections. The intake of zinc, Echinacea preparations (for example: E. purpurea), vitamin C and garlic showed moderate success in the prevention of infection and must be elicited individually. Pneumococcal and annual influenza vaccines in family practice should be given furthermore accordingly topical STIKO-recommendation. Nevertheless, the prophylactic effect from influenza vaccines on usual cold illnesses is unsettled.

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism.

BACKGROUND: Prenatal infection is a substantial risk factor for neurodevelopmental disorders such as autism in offspring. We have previously reported that influenza vaccination (VAC) during early pregnancy contributes to neurogenesis and behavioral function in offspring. RESULTS: Here, we probe the efficacy of VAC pretreatment on autism-like behaviors in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) mouse model. We show that VAC improves abnormal fetal brain cytoarchitecture and lamination, an effect associated with promotion of intermediate progenitor cell differentiation in MIA fetal brain. These beneficial effects are sufficient to prevent social deficits in adult MIA offspring. Furthermore, whole-genome analysis suggests a strong interaction between Ikzf1 (IKAROS family zinc-finger 1) and neuronal differentiation. Intriguingly, VAC rescues excessive microglial Ikzf1 expression and attenuates microglial inflammatory responses in the MIA fetal brain. CONCLUSIONS: Our study implies that a preprocessed influenza vaccination prevents maternal bacterial infection from causing neocortical lamination impairments and autism-related behaviors in offspring.

The Vaccination Model in Psychoneuroimmunology Research: A Review.

This chapter explores the reasoning behind using the vaccination model to examine the influence of psychosocial factors on immunity. It then briefly discusses the mechanics of the vaccination response and the protocols used in psychoneuroimmunology vaccine research, before giving examples from the research literature of the studies examining relationships such as the association between stress and vaccination response. It also explores the ways the vaccination model can be used to answer key questions in psychoneuroimmunology, such as the following: "Does it matter when stressful life events occur relative to when the vaccine is received?" "What are the effects of prior exposure to the antigen?" "Do other psychosocial factors influence vaccine response besides stress?" Finally, it briefly considers the mechanisms underlying psychosocial factors and vaccination response associations and the future research needed to understand these better, and indeed to use current and future knowledge to improve and enhance vaccine responses in key at-risk populations.

Positive mood on the day of influenza vaccination predicts vaccine effectiveness: A prospective observational cohort study.

Influenza vaccination is estimated to only be effective in 17-53% of older adults. Multiple patient behaviors and psychological factors have been shown to act as 'immune modulators' sufficient to influence vaccination outcomes. However, the relative importance of such factors is unknown as they have typically been examined in isolation. The objective of the present study was to explore the effects of multiple behavioral (physical activity, nutrition, sleep) and psychological influences (stress, positive mood, negative mood) on the effectiveness of the immune response to influenza vaccination in the elderly. A prospective, diary-based longitudinal observational cohort study was conducted. One hundred and thirty-eight community-dwelling older adults (65-85years) who received the 2014/15 influenza vaccination completed repeated psycho-behavioral measures over the two weeks prior, and four weeks following influenza vaccination. IgG responses to vaccination were measured via antigen microarray and seroprotection via hemagglutination inhibition assays at 4 and 16weeks post-vaccination. High pre-vaccination seroprotection levels were observed for H3N2 and B viral strains. Positive mood on the day of vaccination was a significant predictor of H1N1 seroprotection at 16weeks post-vaccination and IgG responses to vaccination at 4 and 16weeks post-vaccination, controlling for age and gender. Positive mood across the 6-week observation period was also significantly associated with post-vaccination H1N1 seroprotection and IgG responses to vaccination at 16weeks post-vaccination, but in regression models the proportion of variance explained was lower than for positive mood on the day of vaccination alone. No other factors were found to significantly predict antibody responses to vaccination. Greater positive mood in older adults, particularly on the day of vaccination, is associated with enhanced responses to vaccination.

Vaccination in pregnancy: Attitudes of nurses, midwives and health visitors in England.

OBJECTIVE: To examine amongst healthcare professionals in England; knowledge of vaccinations in pregnancy, their perceived roles in these programmes and whether they recommend scheduled vaccines to pregnant women. DESIGN: Cross sectional survey (online questionnaire) Setting: Healthcare workers in contact with pregnant women in England. PARTICIPANTS: The survey analysis included 3441 healthcare workers who had been surveyed during May to August 2015. The participants were midwives, practice nurses and health visitors, working in England who were members of the Royal College of Midwives, Royal College of Nursing and the Institute of Health Visiting. RESULTS: We found that knowledge of vaccination in pregnancy was high in all professional groups. Seventy three percent of all respondents would recommend the influenza vaccine and 74% would recommend the pertussis vaccine to pregnant women. They were more likely to recommend vaccination in pregnancy if they would personally have the influenza and pertussis vaccines themselves and/or if they had the influenza vaccine as a healthcare worker. Practice nurses were significantly more likely to recommend the pertussis and influenza vaccines to pregnant women than midwives and health visitors. Health professionals who had received immunisation training were more confident in giving advice to pregnant women. CONCLUSION: Immunisation training is essential if healthcare workers are to be informed and confident in effectively delivering the maternal immunisation programme and thus improving uptake of vaccines in pregnancy. These findings are important in tailoring educational programmes and addressing the training needs of different healthcare professional groups.

Training student pharmacists to administer emergency pediatric influenza vaccine: A comparison of traditional vs. just-in-time training.

INTRODUCTION: This study compared traditional training (TT) and just-in-time training (JITT) of P3 student pharmacists regarding interest, confidence, and comfort pre- and post-training (primary objective); and assessment and administration competency (secondary objective) during a simulated influenza vaccination clinic. METHODS: Student pharmacists were randomized 1:1 to receive either TT or JITT, completed pre- and post-training surveys assessing interest, confidence and comfort; and evaluated on performance during a simulated emergency infant vaccination. An infant manikin simulated a child <1 year of age, and an actor role-played the mother. All students received a briefing about the simulated mass vaccination prior to their performance assessment. Survey differences between groups were analyzed by ANOVA. The competency assessment was analyzed by a Chi-square or Fisher's exact test for individual steps and Student t-test for mean scores. RESULTS: Pre-training interest was high and maintained post-training. Pre-training confidence and comfort levels were low and improved in both groups. Mean competency scores were comparable between the TT and JITT groups. Comparing groups, TT students more commonly missed proper injection site selection and care; while JITT missed distracting the infant and administration documentation. DISCUSSION AND CONCLUSIONS: JITT for student pharmacists to learn skills required to immunize infants elicits similar outcomes (interest, confidence, comfort, and administration competency) as TT for emergency pediatric influenza vaccination.

Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens against highly pathogenic avian influenza virus.

Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the best formulations for chickens, vaccines were prepared with beta-propiolactone (BPL) inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially available or experimental adjuvants. Each vaccine formulation was evaluated for immunogenicity in chickens. Challenge studies with an antigenically homologous strain of HPAIV were conducted to compare protection against mortality and measure reductions in virus levels in oral swabs. The four best adjuvants from the studies with BPL inactivated antigen were selected and tested identically, but with vaccines prepared from formalin inactivated virus. Mineral and vegetable oil based adjuvants generally induced the highest antibody titers with 100% seroconversion by 3weeks post vaccination. Chitosan induced positive antibody titers in 100% of the chickens, but the titers were significantly lower than those of most of the oil based adjuvants. Antibody levels from calcium phosphate and alginate adjuvanted groups were similar to those of non-adjuvanted virus. All groups that received adjuvanted vaccines induced similar levels of protection against mortality (0-20%) except the groups vaccinated with calcium phosphate adjuvanted vaccines, where mortality was similar (70%) to groups that received non-adjuvanted inactivated virus or no vaccine (60-100% mortality). Virus shedding in oral swabs was variable among the treatment groups. Formalin inactivated vaccine induced similar antibody titers and protection against challenge compared to BPL inactivated vaccine groups. These studies support the use of oil adjuvanted vaccines for use in the poultry industry for control for AIV.

[Effectiveness of preventive treatment by Influenzinum in the winter period against the onset of influenza-like illnesses]. / Efficacité d'un traitement préventif par Influenzinum en période hivernale contre la survenue d'un syndrome grippal.

AIM: In vitro Influenzinum induce a cellular change. We present the results of the first study examining the effectiveness of Influenzinum against influenza-like illnesses. METHOD: Retrospective cohort study during winter 2014-2015. After influenza epidemic, a self-assessment questionnaire was offered to patients presenting for a consultation. The primary endpoint was the declaration of an influenza-like illness. The exposed patients (treated by Influenzinum) were matched to two non-exposed patients (untreated) with a propensity score. A conditional logistic model expressed influenza-like illness risk reduction provided by the Influenzinum. RESULTS: The cohort included 3514 patients recruited from 46 general practitioners. After matching, the treated group (n=2041) and the untreated group (n=482) did not differ on variables collected. Influenzinum preventive therapy does not significantly alter the likelihood of influenza-like illness (adjusted odds ratio=0,91 [0,62 to 1,35], p=0,64). CONCLUSION: Influenzinum preventive therapy did not appear effective in preventing influenza-like illness.

Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults.

BACKGROUND & AIMS: Mortality resulting from influenza (flu) virus infections occurs primarily in the elderly through declining immunity. Studies in mice have suggested beneficial effects of selenium (Se) supplementation on immunity to flu but similar evidence is lacking in humans. A dietary intervention study was therefore designed to test the effects of Se-supplementation on a variety of parameters of anti-flu immunity in healthy subjects aged 50-64 years. METHODS: A 12-week randomized, double-blinded, placebo-controlled clinical trial (ClinicalTrials.govNCT00279812) was undertaken in six groups of individuals with plasma Se levels <110 ng/mL. Four groups were given daily capsules of yeast enriched with 0 µg Se/day (SeY-0/d; n = 20), 50 µg Se/d (SeY-50/d; n = 18), 100 µg Se/d (SeY-100/d; n = 21) or 200 µg Se/d (SeY-200/d; n = 23). Two groups were given onion-containing meals with either <1 µg Se/d (SeO-0/d; n = 17) or 50 µg Se/d (SeO-50/d; n = 18). Flu vaccine was administrated at week 10 and immune parameters were assessed until week 12. RESULTS: Primary study endpoints were changes in cellular and humoral immune responses. Supplementation with SeY and SeO affected different aspects of cellular immunity. SeY increased Tctx-ADCC cell counts in blood (214%, SeY-100/d) before flu vaccination and a dose-dependent increase in T cell proliferation (500%, SeY-50/100/200/d), IL-8 (169%, SeY-100/d) and IL-10 (317%, SeY-200/d) secretion after in vivo flu challenge. Positive effects were contrasted by lower granzyme B content of CD8 cells (55%, SeY-200/d). SeO (Se 50 µg/d) also enhanced T cell proliferation after vaccination (650%), IFN-γ (289%), and IL-8 secretion (139%), granzyme (209%) and perforin (190%) content of CD8 cells but inhibited TNF-α synthesis (42%). Onion on its own reduced the number of NKT cells in blood (38%). These effects were determined by comparison to group-specific baseline yeast or onion control groups. Mucosal flu-specific antibody responses were unaffected by Se-supplementation. CONCLUSION: Se-supplementation in healthy human adults with marginal Se status resulted in both beneficial and detrimental effects on cellular immunity to flu that was affected by the form of Se, supplemental dose and delivery matrix. These observations call for a thorough evaluation of the risks and benefits associated with Se-supplementation.

Respiratory Conditions Update: Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is defined as persistent airflow limitation due to irritant-induced chronic inflammation. A postbronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio of 0.7 or less is diagnostic in a patient with dyspnea, chronic cough or sputum production, and a history of irritant exposure. Tobacco smoking is the most significant etiology, and smoking cessation is the only intervention shown to slow disease progression. Long-acting beta2-agonists and long-acting muscarinic antagonists are first-line treatments for patients with persistently symptomatic COPD with an FEV1 of 80% or less of predicted. When COPD is uncontrolled with a long-acting bronchodilator, combination therapy with a long-acting muscarinic antagonist-long-acting beta2-agonist or long-acting beta2-agonist-inhaled corticosteroid should be prescribed. Patients with COPD and reduced exercise tolerance should undergo pulmonary rehabilitation and be evaluated for supplemental oxygen therapy. Other treatment options for persistently symptomatic COPD include inhaler triple therapy (ie, long-acting muscarinic antagonist, long-acting beta2-agonist, inhaled corticosteroid), phosphodiesterase type 4 inhibitors, oxygen, and surgical interventions.

Respiratory Conditions Update: Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal recessive genetic disease that occurs in approximately 1 in 2,500 white live births. It is less common in nonwhite individuals. A dysfunctional epithelial chloride channel leads to excessively thick mucus affecting multiple organ systems. Common issues include mucous plugging of the airway, lung inflammation, chronic pulmonary infections, intestinal malabsorption, and malnutrition. Universal screening of newborns for CF is recommended in many countries. CF can be diagnosed based on clinical evidence of disease along with genetic testing or other laboratory evidence of chloride channel dysfunction. Pulmonary system dysfunction causes the most morbidity and mortality. Pulmonary function testing is the primary modality used to monitor CF progression. Therapies include chest physiotherapy, mucolytics, antibiotics, anti-inflammatory drugs, targeted therapies, and vaccines. Dysfunction of the exocrine pancreas and gastrointestinal tract leads to malabsorption, malnutrition, and intestinal obstruction. Nutrition should be optimized with adequate calories, pancreatic enzymes, and appropriate dietary supplements. Complications, including acute pulmonary exacerbations, gastrointestinal conditions, chronic rhinosinusitis, CF-related diabetes, osteoporosis, infertility, and psychosocial issues, must be managed. At the appropriate time, lung transplantation and end-of-life issues must be addressed.

Immunotherapy for non-responders among patients of spinal tuberculosis.

BACKGROUND: Combined chemo- and immunotherapy are the major advancement in the treatment of tuberculosis. Immunotherapy supposedly increases cure rate while reducing the duration of treatment and tissue damage. Non-responders are those patients of tuberculosis who do not respond to anti-tubercular therapy (ATT) in the desired manner despite the mycobacteria showing sensitivity to the given drugs. The role of immunotherapy in the treatment of this particular subset of patients has been investigated scarcely. METHODS: The present study included a retrospective review of prospectively collected clinico-radiological data of 14 non-responder patients who were taking ATT for spinal tuberculosis for a mean duration of 10.3 months. An immunotherapeutic regime comprising of single intramuscular injection of vitamin D 600,000IU, 3 days course of oral albendazole 200mg daily, salmonella vaccine 0.5ml intramuscular and influenza vaccine 0.5ml intramuscular were added to ATT. The vaccines and the course of oral albendazole were repeated after a month. RESULTS: Before immunotherapy, seven patients were partially dependent while other seven were completely dependent on others for activities of daily living. All except one patient after treatment became independent till last follow-up (p value <0.01). Post immunotherapy, ATT was continued for mean duration of 4.9 months with mean follow-up of 22.4 months. All patients showed good clinical response within 2-6 weeks after the initiation of immunotherapy. CONCLUSIONS: The crux to success of the immunotherapy regime is its potential to restore the existing Th1 Th2 imbalance and to provide substitute to the anergic and dysfunctional immune cells.

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies.

Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: (1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and (2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48-0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32-0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15mcg had the highest estimated theoretical vaccine efficacy: Dose (1) 45% (95% CI: 36-57%), 53% (95% CI: 42-63%) and 55% (95% CI: 44-64%), respectively and Dose (2) 93% (95% CI: 89-96%), 97% (95% CI: 95-98%) and 97% (95% CI: 96-100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals against a potential avian influenza pandemic.