Comparing influenza vaccine effectiveness between cell-derived and egg-derived vaccines, 2017–2018 influenza season

The Department of Defense Global Respiratory Pathogen Surveillance Program conducted a study to compare the differences in vaccine effectiveness (VE) of the cell-derived and egg-derived vaccines. DoD healthcare beneficiaries, excluding service members, that presented with influenza-like illness for the period of 1 October 2017 through 28 April 2018 were included in a test-negative case-control study examining laboratory confirmed influenza infections. Three VE analyses were performed (1) influenza infection among those vaccinated with cell-derived vaccines (2) influenza infection among those vaccinated with egg-derived vaccines and a (3) relative VE which directly compared the odds of influenza infection with cell-derived vaccine against those with egg-derived vaccines. The cell-derived and egg-derived vaccines were moderately protective against all influenza types with significant VE estimates for all dependents at 46% (95% confidence interval, 33, 56) and 53% (45, 60), respectively. Of the subtype analyses, influenza A(H1N1)pdm09 performed the best. In the cell-derived vaccine, the adult age group was moderate to high at 71% (44, 85) and children moderate at 56% (15, 75). In the egg-derived vaccine, the children age group was at a high 88% (80, 93) effectiveness and adults at 81% (56, 92). When comparing cell-derived vaccine directly to the egg-derived vaccine, the relative VE found significant results only for influenza A(H1N1)pdm09 which favored the egg-derived vaccine with odds ratios of 2.0 (1.1, 3.6) for all dependents and 2.9 (1.3, 6.3) for children. In the influenza A(H3N2) analysis, statistical significance was not gained; however, the odds favored the cell-derived vaccine.     

Report of the 6th meeting on the evaluation of pandemic influenza vaccines in clinical trials World Health Organization,Geneva, Switzerland, 17–18 February 2010

On February 17–18, 2010, the World Health Organization (WHO) convened the 6th meeting on the “Evaluation of pandemic influenza vaccines in clinical trials” to review the progress made on new A (H1N1) 2009 vaccines and prototype H5N1 vaccines and their evaluation in clinical trials. A number of vaccine types were reviewed, including classical egg-derived and cell culture-derived inactivated vaccines, such as split virus or whole-virion vaccines, and live-attenuated vaccines (LAIV), as well as vaccines developed using new technologies. The amount of antigen needed, the effect of adjuvants and the number of doses required to induce adequate antibody responses in various populations, together with the issue of safety of the vaccines, were major topics of the meeting. The effectiveness of H1N1 vaccines and the need for standardization of vaccine potency tests were also discussed. Independent of the vaccine type and the presence or absence of an adjuvant, all A (H1N1) 2009 vaccines were well tolerated, eliciting only mild to moderate local or systemic reactions. For most vaccines tested, a single dose was sufficient to elicit a potentially protective antibody response in the majority of vaccinees >10 years of age. However, a second dose of vaccine was needed to boost immune responses in infants and toddlers 6 months to 3 years of age and, with some vaccines, in children aged 3–9 years.     

Assessment of the immunogenicity and safety of varying doses of an MF59®-adjuvanted cell culture-derived A/H1N1 pandemic influenza vaccine in Japanese paediatric, adult and elderly subjects

Introduction

Effective vaccination strategies are required to combat future influenza pandemics. Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity, tolerability and safety of varying doses of a cell culture-derived MF59^®-adjuvanted A/H1N1 pandemic vaccine in healthy Japanese paediatric, adult and elderly subjects.

Methods

One hundred and twenty-three children (6 months–18 years), and 200 adults (19–60 years) were randomly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7.5 μg antigen with a full (9.75 mg) adjuvant dose, or 3.75 μg antigen with a half (4.875 mg) adjuvant dose. One hundred elderly (≥61 years) subjects received only the low antigen/adjuvant vaccine formulation. Immunogenicity was assessed by haemagglutination inhibition assay at baseline and three weeks after the first and second vaccine doses on Days 22 and 43, respectively. Solicited and unsolicited adverse reactions were recorded for seven and 21 days post-immunization, respectively.

Results

In adult and elderly subjects, a single low antigen/adjuvant dose vaccination was sufficient to meet all of the three European licensure criteria established for influenza vaccines. One high, or two low antigen/adjuvant dose vaccinations were required to meet the licensure criteria in paediatric subjects. Both vaccine formulations were well tolerated, with the majority of adverse reactions mild to moderate in severity. None of the five serious adverse events reported throughout the three trials were considered to be vaccine-related by the investigators.

Conclusion

The use of MF59 adjuvant allows for much reduced vaccine antigen content, and a single dose administration schedule in adults and the elderly. The production of pandemic vaccine using modern cell culture techniques is highly advantageous in terms of the quantity, quality, and rapidity of antigen production; these benefits, in combination with the use of MF59, maximize manufacturing capacity and global vaccine supply. These data support the suitability of the investigational vaccine for use in the Japanese paediatric, adult, and elderly populations.     

Immunogenicity and safety of a cell culture-derived inactivated trivalent influenza vaccine (NBP607): A randomized,double-blind,multi-center,phase 3 clinical trial

BackgroundCell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity.MethodsA randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (Agrippal^®S1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number—NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination.ResultsA total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups.ConclusionNBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine.     

Safety,immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children,adolescents, and adults: A randomized,controlled, phase III trial

BackgroundInactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate.MethodsThis phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination.Results1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains.ConclusionsIn both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity criteria for adults.Clinical trial registry numberNCT01481454.     

Clinical development of a Vero cell culture-derived seasonal influenza vaccine

Background

Cell culture technologies have the potential to improve the robustness and flexibility of influenza vaccine supply and to substantially shorten manufacturing timelines. We investigated the safety, immunogenicity and efficacy of a Vero cell culture-derived seasonal influenza vaccine and utilized these studies to establish a serological correlate of vaccine protection.

Methods

Two multicenter, randomized, double-blind phase III trials were undertaken in the US during the 2008–2009 Northern hemisphere influenza season, in young (18–49 years) and older (50–64 years and ≥65 years) adult subjects. 7250 young adults were randomized 1:1 to receive either Vero-derived vaccine or placebo. 3210 older adult subjects were randomized 8:1 to receive either Vero-derived vaccine or a licensed egg-derived vaccine. Serum hemagglutination inhibition antibody titers were assessed 21 days post-vaccination. Vaccine efficacy in preventing cell culture-confirmed influenza infection was determined for the young adult population. Local and systemic adverse events were recorded in both studies.

Results

The Vero-derived vaccine was safe and well tolerated in both young and older adults. All US and European immunological licensing thresholds were comfortably met in both populations. Vaccine efficacy in young adults was 79% against A/H1N1 viruses antigenically matching the corresponding vaccine strain and 78.5% for all antigenically matched influenza viruses. A hemagglutination inhibition antibody titer of ≥1:15 provided a reliable correlate of protection for the Vero-derived influenza vaccine, with no additional benefit at titers >1:30. Bridging of the correlate of protection established in the young adult population to the older adult immunogenicity data demonstrated the likely effectiveness of the Vero-derived vaccine in the older adult population.

Conclusions

A Vero cell culture-derived seasonal influenza vaccine is safe, immunogenic and protects against infection with influenza virus. The novel vaccine technology has the potential to make a substantial contribution to improving influenza vaccine supply.

Clinical trial registration

The studies are registered with ClinicalTrials.gov, numbers NCT00566345 and NCT00782431.     

Immunogenicity and safety of three consecutive lots of a new preservative-free inactivated hepatitis A vaccine (Healive): a double-blind, randomized and controlled trial

Immunization is considered as the most effective way for the prophylaxis of hepatitis A virus (HAV) infection. This study aimed to evaluate the immunogenicity and safety of three consecutive lots of a new preservative-free inactivated hepatitis A vaccine (Healive) in healthy children. A double-blind, randomized and controlled clinical trial was conducted in healthy volunteers aged from 1 to 8 years. Total 400 subjects were enrolled and assigned into four groups, receiving one of the three lots of Healive or an established control vaccine. The vaccination was two-dose regimen with 6 months apart. Anti-HAV titers were determined at the 1st, 6th and 7th month. The results showed that Healive was highly immunogenic in children with 100% seroconversion rate (SR) and 3237-3814 mIU/ml geometry mean titer (GMT) 1 month after the second dose. The immunogenicity of Healive was statistically higher than that of the control vaccine with respect to GMT and SR (P=0.037 to P<0.001). Both Healive and control vaccine were well tolerated with 1-5% incidence of overall adverse reactions (P>0.298). Severe adverse reaction was not reported. Both SRs (1, 6 and 7 months) and GMTs (1 and 7 months) in subjects receiving one of the three consecutive lots of Healive had not statistical difference (P=0.114-0.710), suggesting that Healive was well consistent. The immune responses in younger children (1-3 years) and older children (4-8 years) were similar to each other (P=0.187-0.963). The present study indicated that Healive was greatly consistent between production lots, well tolerated and highly immunogenic in children, which made the preservative-free inactivated hepatitis A vaccine well suitable for inclusion in the routine programme of children vaccination.     

Diphtheria antitoxin response to DTP vaccines used in Swedish pertussis vaccine trials, persistence and projection for timing of booster

Data from two Swedish pertussis vaccine trials with various combination vaccines were used to compare anti-diphtheria antitoxin concentrations over time between different vaccines, vaccine lots and vaccine schedules. The immune responses were measured with a validated ELISA method.Results are given for 1326 children, born 1992, that were recruited to the placebo (DT)-controlled Trial I which used a 2, 4, 6 month schedule. Two DTP acellular and one DTP whole cell vaccine were used. No DT boosters were given until 5 years of age.Trial II recruited children born 1993-94 and compared three DTP acellular vaccines with one DTP whole cell vaccine. Results are given for 306 children in a 2, 4, 6 month schedule and for 531 children in a 3, 5, 12 month schedule. The latter schedule gave significantly higher diphtheria antitoxin concentrations post third dose.The various DTP acellular vaccines and an inefficacious DTP whole cell vaccine gave lower antitoxin concentrations than both an efficacious DTP whole cell vaccine and the DT vaccine. The larger differences in antigen response between vaccines was reduced in the course of time. Generally, an initial rapid decline of antitoxin concentration was followed by a slower decline; the change typically occurring when the antitoxin concentration reached 0.13-0.16 EU/ml. The time needed to reach this level was between 6 and 10 months based on the initial vaccine response.A "best-fit" combined exponential regression model was used to predict the optimal timing for booster vaccinations against diphtheria.Our data support a 3, 5, 12 month schedule followed by a fourth dose 4-5 years after the third dose, depending upon the vaccine used.     

Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi adults and children

We have compared the B cell responses evoked in Bangladeshi, adults (n=11, median age 25 years) and children (n=21, median age 4.5 years), 7 days after intake of each of two doses of an oral, inactivated enterotoxigenic Escherichia coli (ETEC) vaccine composed of formalin-killed ETEC strains expressing the colonization factors, CFA/I, CFA/II and CFA/IV together with 1 mg of recombinant cholera toxin B-subunit (rCTB). The vaccine was well tolerated and only gave rise to negligible side effects. Peak antibody-secreting cell (ASC) response of the IgA isotype were seen 7 days after the first dose of the vaccine. The ASC responses to the different colonization factors (CFs) increased from a 29- to 46-fold (responder frequency 90-100%) in the adults and 13- to 24-fold (responder frequency 67-90%) in the children. The IgA-ASC response to rCTB also peaked after the first dose in the adults (426-fold, responder frequency 100%) and the children (46-fold, responder frequency 95%). Increased IgA antibody levels against CFA/I as well as IgA and IgG antibody levels to rCTB were seen in plasma after immunisation. About 86% of the children and 80% of the adults responded with faecal antibodies to rCTB, whereas about 67% of both groups responded to CFA/I.These results show that a single dose of the ETEC vaccine may elicit significant mucosal immune responses in both children and adults residing in an ETEC-endemic country such as Bangladesh.     

Annual report on surveillance of adverse events following immunisation in Australia, 2006

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) reported to the Adverse Drug Reactions Advisory Committee for 2006, and describes reporting trends over the seven-year period 2000 to 2006. There were 779 AEFI records for vaccines administered in 2006. This is an annual AEFI reporting rate of 3.8 per 100,000 population, the lowest since 2002 and a 10% decrease compared with 2005 (869 AEFI records; 4.3 records per 100,000 population). Dose-based AEFI reporting rates in 2006 were 1.9 per 100,000 doses of influenza vaccine for adults aged > or = 18 years, 19.1 per 100,000 doses of pneumococcal polysaccharide vaccine for those aged > or = 65 years and 12.5 per 100,000 doses of scheduled vaccines for children aged < 7 years. Trend data showed transient increases in reporting of AEFI following the introduction of DTPa-IPV combination vaccines in November 2005 for children aged < 7 years. The majority of the 779 AEFI records for 2006 described non-serious events while 11% (n = 85) described AEFIs defined as serious. There was one report of death temporally associated with receipt of dTpa-IPV and typhoid vaccines in an adult with a history of a chronic medical condition. The most frequently reported individual AEFI was injection site reaction in children following a fourth or fifth dose of acellular pertussis-containing vaccine (70 reports per 100,000 doses). The data confirm the low rate of AEFI reported in Australia and demonstrate the ability of the system to detect and investigate signals such as those associated with changes in immunisation programs.     

Safety and immunogenicity of the modified adult tick-borne encephalitis vaccine FSME-IMMUN: results of two large phase 3 clinical studies

A prospective, randomised, multicentre, single-blind phase 3 study was performed to assess the safety of a vaccination schedule consisting of two vaccinations (21-35 days apart) with the tick-borne encephalitis (TBE) vaccine FSME-IMMUN "adults" (five consecutive lots) in comparison to another licensed TBE vaccine (Encepur), with polygeline) (two lots) in healthy volunteers (n=3966) aged 16-65 years. The safety of the third vaccination with FSME-IMMUN "adults" (6 months after the first vaccination) was investigated in a follow-up study on the same population (n=3705) and TBE antibody titres were analysed pre- and post-vaccination in a subgroup of volunteers (n=564). Following the first vaccination, the overall incidence of fever (> or =38.0 degrees C) was 0.8% in the FSME-IMMUN "adults" study group and 5.6% in the comparator study group; fever was mainly mild. The fever rate after the second vaccination was 0.6% and 0.5% in the two study groups, respectively. Local and systemic reactions after the first vaccination occurred with a lower frequency in the FSME-IMMUN "adults" study group than in the comparator group. Upon analysing the tolerability of the third vaccination with FSME-IMMUN "adults", similar results were determined in both study groups of volunteers previously vaccinated with FSME-IMMUN "adults" or with the comparator vaccine. The immunogenicity results demonstrated similar seroconversion rates (as determined by ELISA or neutralization test) before and after the third vaccination in the FSME-IMMUN "adults" group and in the comparator group respectively. The results of both studies demonstrate that: (1) FSME-IMMUN "adults" is safe and highly immunogenic, (2) all five production lots of FSME-IMMUN "adults" were consistent with respect to a low rate of adverse events, (3) FSME-IMMUN "adults" induces considerably lower adverse reaction rates than the comparator vaccine after the first vaccination, and (4) two vaccinations with the comparator vaccine can be successfully followed by a third vaccination with FSME-IMMUN "adults".     

成年人连续三批次流感裂解疫苗接种的安全性、免疫原性观察

目的 评价流感裂解疫苗安尔来福TM的安全性和免疫原性,考核疫苗生产工艺的稳定性.方法 采用随机双盲设对照的临床试验设计,试验疫苗为连续三个批次的安尔来福TM,以进口疫苗为对照.受试者为566名18～60岁健康成年人,按照4个年龄层随机分配到4个试验组,疫苗含甲1型、甲3型和乙型流感病毒抗原各15 μg.免疫程序为1针,接种后进行30 min即时反应观察以及24、48、72 h的随访观察,免疫前及免疫后第21天采血,将成对血清设盲后进行血凝抑制(HI)抗体检测.结果 受试者以轻度不良反应为主,各试验组发热反应发生率为1.4%～2.8%,组间差异无统计学意义.4个组3个型别HI抗体阳转率均≥80.3%,GMT增长倍数≥11.1,抗体保护率≥93.4%.三个批次安尔来福TM3个型别的HI抗体阳转率、GMT增长倍数及血清抗体保护率均超过欧盟及美国FDA标准.结论 连续三批次安尔来福TM具有良好的免疫原性和安全性,疫苗生产工艺稳定.     

Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya

We report the first trial of candidate malaria vaccine antigen FMP1, a 42kDa fragment from the C-terminus of merozoite surface protein-1 (MSP-1) from the 3D7 strain of Plasmodium falciparum, in an endemic area. Forty adult male and female residents of western Kenya were enrolled to receive 3 doses of either FMP1/AS02A or Imovax rabies vaccine by intra-deltoid injection on a 0, 1, 2 month schedule. Thirty-seven volunteers received all three immunizations and 38 completed the 12-month evaluation period. Slightly more recipients of the FMP1/AS02A vaccine experienced any instance of pain at 24 h post-immunization than in the Imovax group (95% versus 65%), but otherwise the two vaccines were equally safe and well-tolerated. Baseline antibody levels were high in both groups and were boosted in the FMP1/AS02A group. Longitudinal models revealed a highly significant difference between groups for both the average post-baseline antibody responses to MSP-1(42) (F1,335=13.16; P<0.001) and the Day 90 responses to MSP-1(42) (F1,335=16.69; P<0.001). The FMP1/AS02A vaccine is safe and immunogenic in adults and should progress to safety testing in children at greatest risk of malaria.     

Annual report: surveillance of adverse events following immunisation in Australia, 2010

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) reported to the Therapeutic Goods Administration (TGA) for 2010, and describes reporting trends over the 11-year period 2000 to 2010. There were 3,894 AEFI records for vaccines administered in 2010, the highest number reported in any year, and a 63% increase over the 2,396 in 2009. The increase was almost entirely attributable to the large number of reports following seasonal influenza (n = 2,354) and pandemic H1N1 (pH1N1) influenza vaccines (n = 514). In children < 7 years of age, the number of reports following influenza vaccine increased almost 100-fold from 17 in 2009 to 1,693 in 2010 and, for people aged > or =18 years, from 135 to 496. For seasonal influenza vaccine, a disproportionate number of reports were from Western Australia (34%), consistent with more widespread influenza vaccination of children in that state, and 79% were identified as being associated with Fluvax or Fluvax junior (CSL Biotherapies). For pH1N1 vaccine, the number of reports in children < 7 years of age increased from 23 in 2009 to 329 in 2010, but was available for this age group for only 1 month (December) in 2009. In those aged > or = 18 years, for whom the pH1N1 vaccine was available from late September 2009, pH1N1 vaccine reports decreased from 1,209 in 2009 to 109 in 2010. For influenza vaccines, 79% of reports included fever, 45% allergic reactions and 15% malaise. In children aged < 7 years, there were 169 reports of convulsions (127 febrile), compared with 19 in 2009. In contrast, for non-influenza vaccines, reporting rates in children < 7 years of age increased only marginally from 14.1 per 100,000 in 2009 to 19.3 per 100,000 in 2010. Four deaths temporally associated with immunisation were reported but none were considered to have a causal association.     

甲肝灭活疫苗(Vero细胞)在2岁以上中国健康人群的免疫原性和安全性研究

目的比较甲型肝炎(甲肝)灭活疫苗(Vero细胞)与甲肝灭活疫苗(二倍体细胞)在2岁以上健康人群中的免疫原性和安全性。方法采用随机、盲法、对照的设计,选择2 100名2岁以上甲肝易感者,分为A、B两组,按照0、6月免疫程序,接种甲肝灭活疫苗(Vero细胞)或甲肝灭活疫苗(二倍体细胞)并观察安全性;所有受试者于免前、全程免后1个月采血(前600名还需采集首剂免疫后1个月血样),采用间接酶联免疫吸附试验方法(ELISA)检测抗甲肝病毒抗体(抗-HAV),评价免疫效果。结果 1剂后A组抗-HAV阳转率为96.05%(成人)和92.78%(儿童),B组为94.92%(成人)和96.61%(儿童);2剂后A组为99.61%(成人)和99.53%(儿童),B组为99.41%(成人)和100.00%(儿童)。两组间抗-HAV阳转率均无统计学差异。安全性方面,A组不良反应率为32.41%(成人)和53.61%(儿童),B组为35.56%(成人)和53.33%(儿童),1级反应为主,组间无统计学差异。结论甲肝灭活疫苗(Vero细胞)对2岁以上的人群免疫原性和安全性良好。     

Seasonal influenza vaccine delivered by intradermal microinjection: A randomised controlled safety and immunogenicity trial in adults

Influenza vaccines remain largely underused. A promising alternative to current intramuscular vaccines is a trivalent inactivated influenza vaccine (TIV) delivered using a microinjection system to offer a less invasive and possibly more acceptable vaccination. A phase II, multicentre, randomised open-label study in 978 healthy adults (18-57 years) evaluated the immunogenicity and safety of intradermal TIV. Subjects received a 0.1 ml injection of intradermal TIV, containing 9 microg of haemagglutinin (HA) per strain (n = 588) or a conventional 0.5 ml intramuscular vaccine (15 microg of HA/strain; n = 390). Intradermal TIV induced non-inferior humoral immune responses against all three strains and superior responses against both A strains (H1N1, H3N2) compared with the control. Both vaccines were well tolerated.     

Humoral and cell-mediated immunity to vero cell-derived influenza vaccine

A candidate trivalent influenza whole virus vaccine produced in a continuous mammalian cell line (Vero), and analogous commercially available egg-derived vaccines, were compared for their ability to induce humoral and cell-mediated immunity in Balb/c mice. Substantial haemagglutination-inhibition titre and high levels of influenza virus-specific IgG were found in all groups of immunized mice, irrespective of the vaccine formulation. The IgG responses were predominantly of IgG1 and IgG2a/2b isotypes. Virus-specific secretory IgA antibodies were detected only in mice immunized intranasally with a live virus, derived either from Vero cells or eggs. T-cell proliferative responses and T-helper 1 type cytokine release was significantly higher in mice immunized with Vero cell-derived influenza vaccine compared to egg-derived vaccine formulations. We have demonstrated that the immunogenicity of the trivalent Vero cell-derived whole influenza virus vaccine was comparable to that of the equivalent egg-derived vaccine, with respect to humoral immune response and was superior with respect to cellular response.     

A randomized phase 3 trial to assess the immunogenicity and safety of 3 consecutively produced lots of freeze-dried MVA-BN® vaccine in healthy adults

Since vaccination remains the only effective protection against orthopox virus-induced diseases such as smallpox or monkeypox, the strategic use and stockpiling of these vaccines remains of significant public health importance. The approved liquid-frozen formulation of Bavarian Nordic's Modified Vaccinia Ankara (MVA-BN) smallpox vaccine has specific cold-chain requirements, while the freeze-dried (FD) formulation of this vaccine provides more flexibility in terms of storage conditions and shelf life.In this randomized phase 3 trial, the immunogenicity and safety of 3 consecutively manufactured lots of the FD MVA-BN vaccine was evaluated. A total of 1129 healthy adults were randomized to 3 treatment groups (lots 1 to 3) and received 2 vaccinations 4 weeks apart.For both neutralizing and total antibodies, a robust increase of geometric mean titer (GMT) was observed across all lot groups 2 weeks following the second vaccination, comparable to published data. For the primary results, the ratios of the neutralizing antibody GMTs between the lot group pairs ranged from 0.936 to 1.115, with confidence ratios well within the pre-specified margin of equivalence. Results for total antibodies were similar. In addition, seroconversion rates were high across the 3 lots, ranging between 99.1 % and 99.7 %.No safety concerns were identified; particularly, no inflammatory cardiac disorders were detected. The most common local solicited adverse events (AEs) reported across lot groups were injection site pain (87.2%) and erythema (73.2%), while the most common general solicited adverse events were myalgia, fatigue, and headache in 40.6% to 45.5% of all participants, with no meaningful differences among the lot groups. No related serious AEs were reported.In conclusion, the data demonstrate consistent and robust immunogenicity and safety results with a freeze-dried formulation of MVA-BN.Clinical Trial Registry Number: NCT03699124.     

Live attenuated influenza virus vaccines: new options for the prevention of influenza

Live attenuated influenza virus (LAIV) vaccines present new possibilities for the prevention and control of influenza. Administered intranasally, LAIV vaccines offer a needle-free route of administration. These investigational vaccines have also been shown to be safe and effective in children and healthy working adults. A 2-year placebo-controlled trial among young children (1996-1997 and 1997-1998 influenza seasons) demonstrated that LAIV vaccine was associated with a 92% reduction in laboratory-confirmed cases of influenza. Vaccination also significantly reduced episodes of otitis media and antibiotic use. In a placebo-controlled trial among healthy working adults during the 1997-1998 season, LAIV vaccine significantly reduced episodes of febrile upper respiratory tract illness and illness-associated work loss, health-care use, and antibiotic use. Seventy percent of study participants self-administered the vaccine. An economic analysis of the benefits of LAIV vaccine in this population suggests that the break-even cost for LAIV vaccine and its administration for healthy working adults would be about $39. For both children and healthy adults, LAIV vaccine provided substantial protection during the 1997-1998 season when the predominant circulating virus, the A/Sydney variant, was not contained in the vaccine. Studies are still underway to evaluate the potential incremental benefits of LAIV vaccine in addition to inactivated vaccine in high-risk populations. LAIV vaccines will be an important addition to the armamentarium for fighting influenza.