Immunogenicity and safety of inactivated quadrivalent influenza vaccine in adults: A systematic review and meta-analysis of randomised controlled trials

BackgroundA quadrivalent influenza vaccine (QIV) includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata). The presence of both B lineages eliminate potential B lineage mismatch of trivalent influenza vaccine (TIV) with the circulating strain.MethodsElectronic database searches of Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Scopus and Web of Science were conducted for articles published until June 30, 2015 inclusive. Articles were limited to randomised controlled trials (RCTs) in adults using inactivated intramuscular vaccine and published in English language only. Summary estimates of immunogenicity (by seroprotection and seroconversion rates) and adverse events outcomes were compared between QIV and TIV, using a risk ratio (RR). Studies were pooled using inverse variance weights with a random effect model and the I² statistic was used to estimate heterogeneity.ResultsA total of five RCTs were included in the meta-analysis. For immunogenicity outcomes, QIV had similar efficacy for the three common strains; A/H1N1, A/H3N2 and the B lineage included in the TIV. QIV also showed superior efficacy for the B lineage not included in the TIV; pooled seroprotection RR of 1.14 (95%CI: 1.03–1.25, p = 0.008) and seroconversion RR of 1.78 (95%CI: 1.24–2.55, p = 0.002) for B/Victoria, and pooled seroprotection RR of 1.12 (95%CI: 1.02–1.22, p = 0.01) and seroconversion RR of 2.11 (95%CI: 1.51–2.95, p < 0.001) for B/Yamagata, respectively. No significant differences were found between QIV and TIV for aggregated local and systemic adverse events within 7 days post-vaccination. There were no vaccine-related serious adverse events reported for either QIV or TIV. Compared to TIV, injection-site pain was more common for QIV, with a pooled RR of 1.18 (95%CI: 1.03–1.35, p = 0.02).ConclusionIn adults, inactivated QIV was as immunogenic as seasonal TIV, with equivalent efficacy against the shared three strains included in TIV, and a superior immunogenicity against the non-TIV B lineage.     

Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study on immunogenicity and controlled field trials

B lineage mismatch prompted introduction of quadri-valent influenza vaccines (QIV) with two influenza B viruses representing distinct antigenic lineages. To explore the impact on antibody induction and vaccine effectiveness predicted from antibody (VEab), we performed a systematic literature search on immunogenicity studies conducted to assess antibody superiority of QIV over trivalent influenza vaccine (TIV). Thirteen relevant articles described 31 trials from 2007 and 2013. Log-transformed GMT trial estimates and their variances were converted to clinical protection rates predicted from antibody (PRab). VEab estimates were calculated from pre- and post-vaccination PRab. Without specific pre-vaccination immunity, average VEab was 69% for match, and −4% for lineage mismatch. With increasing pre-vaccination seropositivity, mismatch impact declined to 2%. We also performed an umbrella literature search for randomised controlled trials and test-negative case-control trials with TIV, and estimated vaccine effectiveness against laboratory-confirmed influenza B (VEf). Sixty-eight eligible clinical articles described 110 season-trials from 1965 to 2012, covering seasons with B lineage match (n = 52), lineage drift (n = 15) and lineage mismatch (n = 43). With no pre-vaccination antibody levels determined, we used chance of previous exposure to influenza B (Ppe) as pre-seasonal immunity measure. When Ppe was 0%, average VEf for matched seasons was 67%, and for mismatched seasons 35%, indicating a moderate, yet significant mismatch impact on VEf. With increasing Ppe, mismatch impact declined to 3%. Thus serological and field trials indicate that B lineage mismatch impact is negatively related to pre-seasonal immunity and that the gain of QIV over TIV most benefits infants and children not yet exposed to influenza B.     

A prospective cohort study assessing the reactogenicity of pertussis and influenza vaccines administered during pregnancy

BackgroundPertussis vaccination during pregnancy can prevent 91% of infant infections. In 2015, antenatal pertussis vaccination programs were introduced across Australia.MethodsTo monitor the safety of this program, pregnant women who received trivalent influenza vaccine (TIV) and/or diphtheria-tetanus-acellular pertussis vaccine (dTpa) were surveyed by text message seven days post-vaccination about possible adverse events following immunization (AEFI). Univariate logistic regression models were used to calculate the odds of reporting an AEFI following dTpa compared to TIV. Similar analyses were used to compare AEFI reported by women who received a previous dose of dTpa in 2011/2012 as part of a state-wide cocooning program.ResultsOf 5155 women, 4347 (84.3%) replied; 10.8% indicated they experienced an AEFI. There was no difference in the proportion of women who reported any reaction by vaccine; however, women who received dTpa were more likely to report a local reaction than women who received TIV (7.1% and 3.2%, respectively; OR: 2.29; 95% CI: 1.61–3.26). There was evidence suggesting local reactions were more common among women with a previous dose of dTpa (11.4%) compared to women with no previous dose (6.0%; OR: 2.00; 95% CI: 0.95–4.25); 11 (0.3%) women reported attending a hospital emergency department. Subsequent follow-up indicated symptoms resolved and mother and infant were healthy. There was no difference in the proportion of women attending hospital by vaccine (p > 0.05).DiscussionData on systemic and local reactions following receipt of TIV and dTpa during pregnancy support the safety of antenatal vaccination.     

Influenza bivalent vaccine comprising recombinant H3 hemagglutinin (HA) and H1 HA containing replaced H3 hemagglutinin transmembrane domain exhibited improved heterosubtypic protection immunity in mice

Influenza caused by infection of influenza viruses is still a leading cause of morbidity and mortality in human. Vaccination is the main defense against influenza virus, but current influenza trivalent or quatrivalent vaccines (TIV/QIV) would lose their effectiveness when vaccine strains are mismatched with circulating strains. Our early study showed that recombinant influenza Hx-TM HA proteins containing H3 HA transmembrane domain(TM) had improved immunogenicity and heterosubtypic protection over corresponding wild-type Hx-WT HA proteins. In present study, bivalent vaccines containing H3-WT + Hx-TM were investigated for their immune responses and heterosubtypic protection immunities. The data showed that the bivalent vaccines containing H3-WT and H5-TM or H1-TM had improved immune responses and heterosubtypic protection over the bivalent vaccines containing H3-WT and H5-WT or H1-WT respectively. These results demonstrated that the improved immune responses and heterosubtypic protection of Hx-TM HA proteins could be translated into bivalent vaccines, suggesting a feasible strategy of improving the immune responses and heterosubtypic protection of influenza multivalent vaccines such as TIV and QIV.     

Active SMS-based influenza vaccine safety surveillance in Australian children

IntroductionAustralia’s novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration.MethodsParent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia’s National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles.Results7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p < .001). Meningococcal B vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p < .001). Reported fever was strongly associated with medical attendance (OR: 42.6; 95% Confidence Interval (CI): 25.6–71.0). TIV and QIV safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p < .001)). There was no difference in safety profile between brands.DiscussionActive participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually.     

Safety of Russian-backbone seasonal trivalent,live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh

IntroductionLive-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings.Material and methodsWe conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations.ResultsThree hundred children were randomized and administered LAIV (n = 150) or placebo (n = 150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n = 13 vs. n = 16, p = 0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p = 0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events.ConclusionsIn this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted.     

Immunogenicity,safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children

Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3–14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p < 0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p < 0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p < 0.01 for GMT values and p < 0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile.     

Enhanced humoral response to influenza vaccine in aged mice with a novel adjuvant,rOv-ASP-1

Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus, named O. volvulus activation-associated secreted protein-1 (Ov-ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov-ASP-1 (rOv-ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV + rOv-ASP-1. More importantly, the level of the total IgG in aged mice administered TIV + rOv-ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of rOv-ASP-1 induced a low level of cross-reactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. rOv-ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that rOv-ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly.     

Birth outcomes following immunization of pregnant women with pandemic H1N1 influenza vaccine 2009–2010

BackgroundFollowing the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009–2010.MethodsWe telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009–2010 (n = 5365) in a separate study. Here we assessed preterm birth (<37 weeks), very preterm birth (<32 weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500 g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time.ResultsResults did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37 vs 6.28/100 births), very preterm births (5.30 vs 8.29/1000 births), LBW (4.19 vs 2.90/100 births), very LBW (4.54 vs 5.52/1000 births), small for gestational age (9.99 vs 9.24/1000 births), spontaneous abortion (7.10 vs 6.83/1000 pregnancies), stillbirths (7.10 vs 4.57/1000 pregnancies), and congenital anomalies (2.66 vs 2.43/100 births).ConclusionsAlthough constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009–2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV.     

Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection

BackgroundApproaches to improve the immune response of immunocompromised patients to influenza vaccination are needed.MethodsChildren and young adults (3–21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine.ResultsEighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p = 0.27 and 0.09 after dose 1 and 2, respectively).ConclusionHD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV.     

Fc functional antibody responses to adjuvanted versus unadjuvanted seasonal influenza vaccination in community-dwelling older adults

BackgroundSeasonal influenza vaccination with a standard trivalent influenza vaccine (TIV) induces a modest, and cross-reactive, Fc functional antibody response in older adults. Recent improvements to influenza vaccines include a quadrivalent influenza vaccine (QIV) and a TIV adjuvanted with the squalene-based oil-in-water emulsion MF59.MethodsPre- and post-vaccination serum samples from older adults vaccinated with QIV (n = 27) and adjuvanted TIV (n = 44) were studied using hemagglutination inhibition (HAI) assays and dimeric Fc-gamma receptor IIIa binding ELISAs, as a surrogate of antibody-dependent cellular cytotoxicity (ADCC).ResultsWe found that the unadjuvanted QIV elicited a stronger HAI response against the H1N1 vaccine virus than the adjuvanted TIV. Post-vaccination levels of HA-specific ADCC antibodies were similar for older adults vaccinated with QIV and adjuvanted TIV. The ADCC response to influenza vaccination was largely determined by pre-vaccination or baseline levels of these antibodies, with older adults with low baseline levels of ADCC activity demonstrating greater post-vaccination rises.ConclusionsIn this cohort of community-dwelling older adults, the QIV was at least as good as the adjuvanted TIV in the induction of ADCC and HAI responses. Further studies on how these antibody responses translate to efficacy in preventing influenza infections are warranted.     

Comparison of the immunogenicity and safety of quadrivalent and tetravalent influenza vaccines in children and adolescents

BackgroundChildren and adolescents are susceptible to influenza. Vaccination is the most important strategy for preventing influenza, yet there are few studies on the immunogenicity and safety of quadrivalent inactivated influenza vaccine (QIV) containing two A strains (H1N1 and H3N2) and two B lineages (Victoria and Yamagata). Therefore, to further clarify the immunogenicity and safety of QIV in children and adolescents, a meta-analysis was performed to provide a reference for the development of influenza prevention strategies.MethodsPubMed, EMBASE and Cochrane Library were searched for articles published as of February 12, 2019. Random clinical trials comparing the immunogenicity and safety of QIV and TIV among children and adolescents were selected. The main outcomes were comparisons of immunogenicity (seroprotection rate [SPR] and seroconversion rate [SCR] and adverse events using risk ratios (RRs). The meta-analysis was performed using random-effects models.ResultsAmong the 6 months up to 3 years group, QIV showed a higher SPR for B lineages than for TIV-B/Yamagata, with pooled RRs of 3.07 (95% CI: 2.58–3.66) and 1.06 (95% CI: 1.01–1.11), respectively. For the 3 years through 18 years, QIV had a higher SCR and SPR for the Yamagata lineage than for TIV-B/Victoria, with pooled RRs of 2.30 (95% CI: 1.83–2.88) and 1.16 (95% CI: 1.03–1.30), respectively. Compared to TIV-B/Yamagata, a higher SCR and SPR for the Victoria lineage was found for QIV, with RRs of 3.09 (95% CI: 1.99–4.78) and 1.72 (95% CI: 1.22–2.41), respectively. Regarding adverse events, only pain was more frequently reported for QIV than TIV ; the RR was 1.09 (95% CI: 1.02–1.17).ConclusionsThe immunogenicity of QIV for common ingredients was similar to that of TIV, but the former exhibited significantly higher immunogenicity for the unique lineage. QIV also had the same reliable safety as TIV.     

A Phase III randomised trial of the immunogenicity and safety of quadrivalent versus trivalent inactivated subunit influenza vaccine in adult and elderly subjects,assessing both anti-haemagglutinin and virus neutralisation antibody responses

BackgroundTrivalent influenza vaccines (TIVs) offer substantial protection against matching B-strains, however, protection against alternate-lineage B-strains may be enhanced by adding a second B-strain in quadrivalent influenza vaccines (QIVs). In this Phase III, double-blind, multicentre, randomised study, the immunogenicity and safety of subunit inactivated QIV versus TIV was assessed in adult (aged ≥18 to ≤60 years) and elderly (aged ≥61 years) subjects by analysing a combination of haemagglutinin inhibition (HI) and virus neutralisation (VN).MethodsSubjects (n = 1980) were recruited off season (2015/2016) from 20 centres in five European countries and randomised to receive either QIV (n = 1538), TIV with B-strain of the Victoria lineage (n = 221) or TIV with B-strain of the Yamagata lineage (n = 221). The primary aim was to demonstrate non-inferiority of QIV to TIV for immunogenicity against matched influenza strains based on post-vaccination HI titres. Secondary aims were to show superiority of QIV to TIV for immunogenicity against alternate-lineage B-strains and to characterise the immune response by reverse cumulative distribution (RCD) curves of antibody titres and derived serological parameters for HI and VN. Reactogenicity and occurrence of adverse events were assessed post-vaccination.ResultsQIV elicited a non-inferior immune response for matched strains (upper limit of 95% CI for HI geometric mean ratios [GMRs] <1.5) and a superior response for alternate-lineage B-strains (HI GMRs < 1; p < 0.0001) versus TIV. RCD curves demonstrated that post-vaccination HI and VN titres were higher for QIV versus TIV for both alternate-lineage B-strains. Seroconversion rates and geometric mean fold increases of the VN assay were consistent with the HI assay for all strains in QIV. Reporting rates of local and systemic reactions were similar in both vaccine groups.ConclusionsQIV was non-inferior in immunogenicity to TIV for matched strains and superior to the alternate-lineage B-strains in TIV. Safety and tolerability profiles of QIV and TIV were comparable.     

Immunogenicity and safety of an AS03-adjuvanted H5N1 pandemic influenza vaccine in Korean adults: A phase IV,randomized, open-label,controlled study

BackgroundAS03-adjuvanted H5N1 pandemic influenza vaccines have been assessed in an extensive clinical development program conducted in North America, Europe, and Asia including children from 6 months of age, adults, and elderly adults. We evaluated AS03-H5N1 in Korean adults 18 through 60 years of age.MethodsThis Phase IV, randomized, study was conducted to assess the immunogenicity, reactogenicity, and safety of two doses (3.75 μg of hemagglutinin antigen) of A/Indonesia/5/2005 (H5N1) adjuvanted with AS03 given 21 days apart in Korean adults. Antibody responses were assessed using hemagglutination-inhibition (HI) assays against the vaccine strain and a vaccine-heterologous strain (A/Vietnam/1194/2004) 21 days after the second dose. A control group (safety) received a licensed seasonal inactivated trivalent influenza vaccine (TIV). Reactogenicity was assessed for 7 days after each vaccination, and unsolicited adverse events were assessed for 182 days following vaccination in both study groups (NCT01730378).ResultsAS03-H5N1 was immunogenic and elicited robust HI antibody responses with seroconversion rates of 100% for the vaccine strain and 69.1% for the heterologous strain (N = 81). HI antibody responses fulfilled the European licensure criteria for immunogenicity (primary endpoint). The incidence of local and systemic solicited adverse events (reactogenicity) was higher with AS03-H5N1 than TIV. There was no apparent difference in the rate of unsolicited adverse events in the AS03-H5N1 and TIV groups.ConclusionThe results indicate that AS03-H5N1 vaccine is immunogenic with reactogenicity and safety findings that are consistent with the established profile of AS03-H5N1 vaccine.     

Immunogenicity,reactogenicity, and safety of inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine in healthy adults aged ≥18 years: A phase III,randomized trial

Background

Two influenza B lineages have been co-circulating since the 1980s, and because inactivated trivalent influenza vaccine (TIV) contains only one B strain, it provides little/no protection against the alternate B-lineage. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in healthy adults.

Methods

Subjects received one dose of QIV (lot 1, 2, or 3) or one of two TIVs (B strain from Victoria or Yamagata lineage); randomization was 2:2:2:1:1. Hemagglutination-inhibition assays were performed 21-days post-vaccination; superiority of QIV versus TIV for the alternate B-lineage was demonstrated if the 95% confidence interval (CI) lower limit for the GMT ratio was ≥1.5, and non-inferiority against the shared strains was demonstrated if the 95% CI upper limit for the GMT ratio was ≤1.5. Reactogenicity and safety were assessed during the post-vaccination period. NCT01196975.

Results

Immunogenicity of QIV lots was consistent, QIV was superior to TIV for the alternate B-lineage strain, and QIV was non-inferior versus TIVs for shared strains (A/H1N1, A/H3N2, B-strain). Reactogenicity and safety profile of the QIV was consistent with seasonal influenza vaccines.

Conclusion

QIV provided superior immunogenicity for the added B strain without affecting the antibody response to the TIV strains, and without compromising safety.     

Immunogenicity and safety of concomitant MF59-adjuvanted influenza vaccine and 23-valent pneumococcal polysaccharide vaccine administration in older adults

BackgroundConcomitant administration of influenza and pneumococcal vaccines facilitates their uptake by older adults; however, data on immunogenicity and safety of concomitant administration of adjuvanted trivalent inactivated influenza vaccine (aIIV3) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) have not been reported.MethodsSubjects aged ≥65 years (N = 224) were randomized 1:1:1:1 to receive MF59-aIIV3 alone, MF59-aIIV3 + PPSV23 in contralateral arms, MF59-aIIV3 + PPSV23 in the same arm or PPSV23 alone (Clinical Trial Number – NCT02225327). Hemagglutination inhibition assay and multiplex opsonophagocytic killing assay were used to compare immunogenicity after single or concomitant vaccination.ResultsAll groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroconversion rates and geometric mean fold-increases, irrespective of concomitant vaccinations and injection site. For each pneumococcal serotype, opsonic index (OI) increased markedly after the PPSV23 vaccination, irrespective of the concomitant influenza vaccine. All subjects showed an OI ≥ 8 for serotypes 6B, 18C and 19A post-vaccination, with a suggestion that the ipsilateral concomitant vaccination might be associated with higher OIs for some antigens. Local and systemic adverse events were more common in subjects receiving PPSV23 compared to those receiving aIIV3 alone.ConclusionsNo interference was observed with antibody responses to influenza or pneumococcal antigens when aIIV3 and PPSV23 were administered concomitantly.     

Randomized safety and immunogenicity trial of a seasonal trivalent inactivated split virion influenza vaccine (IVACFLU-S) in healthy young Vietnamese adults

BackgroundUnder the auspices of the World Health Organization (WHO) Global Action Plan, PATH supported evaluation of a trivalent, seasonal inactivated influenza vaccine candidate produced by the Institute of Vaccines and Medical Biologicals (IVAC), a Vietnamese manufacturer.MethodsIn 2015, 60 healthy adult subjects 18–45 years of age were enrolled in a Phase 1, single center, double blind, randomized, placebo-controlled study conducted at a district health center in Thai Binh Province, Vietnam. The study evaluated the overall safety and immunogenicity of a seasonal, trivalent inactivated split virion influenza vaccine. Volunteers were given either vaccine or placebo in a randomized 1:1 ratio.After undergoing screening, eligible volunteers provided their signed consent and were enrolled in the study. On the first day of immunization, randomly chosen volunteers received IVACFLU-S 15 μg (mcg) hemagglutinin of each of the three strains in 0.5 mL or placebo by intramuscular injection. All volunteers were monitored for adverse events and underwent blood testing at screening and Day 8 to assess the vaccine candidate’s safety. Sera obtained before and 21 days after immunization were tested for influenza antibody titers using the hemagglutination-inhibition (HAI) and microneutralization tests (MNT).ResultsVaccine was well tolerated, and there were no serious adverse events reported. HAI and MNT identified serum antibody responses against the three influenza strains in nearly all volunteers who received the vaccine. Overall, serum HAI responses of fourfold or greater were observed in 93 percent, 83 percent, and 77 percent of H1, H3, and B strains, respectively. Seroprotection rates were also very high.ConclusionsIVAC’s seasonal, trivalent influenza vaccine was safe and well tolerated and induced high levels of seroconversion and seroprotection rates. These clinical data are a first step towards demonstrating the feasibility of producing the vaccine locally and that seasonal vaccine production in Vietnam may be an effective strategy for enhancing the global influenza vaccine supply. ClinicalTrials.gov number NCT02598089, October 15, 2015.     

Moving the needle on nursing staff influenza vaccination in long-term care: Results of an evidence-based intervention

PurposeInfluenza vaccination rates among healthcare providers (HCPs) in long-term care facilities (LTCFs) are commonly below the Healthy People 2020 goal of 90%. This study was conducted to develop and evaluate an intervention program designed to increase influenza uptake among HCPs in LTCFs.MethodsThis study was conducted in four Midwestern LTCFs. Baseline interviews, surveys, and administrative data analysis were performed following the 2013–2014 influenza season. Interventions implemented during the 2014–2015 season were based on the health belief and ecological models and included goal-setting worksheets, policy development, educational programs, kick-off events, incentives, a vaccination tracking roster, and facility-wide communication about vaccine uptake among HCPs. Outcomes were evaluated in 2015.ResultsAt baseline, 50% of 726 nursing staff employed during the 2013–2014 influenza season had documented receipt of influenza vaccine (Site A: 34%; Site B: 5%; Site C: 75%; Site D: 62%), and 31% of 347 survey respondents reported absenteeism due to respiratory illness. At follow-up, 85% of HCPs had documented receipt of influenza vaccine (p < 0.01) and 19% of 323 survey respondents reported absenteeism due to respiratory illness (p < 0.01). Vaccination rates among respondents’ family members increased from 31% at baseline to 44% post-intervention (p < 0.01). Reasons for declining vaccination did not change following exposure to educational programs, but HCPs were more likely to recommend vaccination to others after program implementation.ConclusionsVaccination rates among long-term care HCPs and their family members increased significantly and HCP absenteeism decreased after the implementation of multifaceted interventions based on an ecological model. The findings suggest that major increases in HCP vaccination can be achieved in LTCFs. More research is needed to evaluate the impact of increased HCP vaccination on the health and productivity of LTCF employees, their family members, and residents.     

Efficacy and safety of a quadrivalent influenza vaccine in children aged 6–35 months: A global,multiseasonal, controlled,randomized Phase III study

BackgroundChildren are an important target group for influenza vaccination, but few studies have prospectively evaluated influenza vaccine efficacy (VE) in children under 3 years of age. This was a randomized Phase III trial to assess the efficacy, immunogenicity, and safety of an inactivated quadrivalent influenza vaccine (QIV) in young children (EudraCT: 2016–004904–74).MethodsInfluenza-naïve children aged 6–35 months were randomized during three influenza seasons to receive vaccination with QIV or a non-influenza control vaccine. One group of participants was revaccinated with QIV in the subsequent influenza season. The primary efficacy endpoint was the absolute VE of QIV against influenza caused by any circulating strain. Key secondary efficacy endpoints included the absolute VE of QIV against influenza due to antigenically matching strains and immunogenicity. Safety and reactogenicity were also evaluated.ResultsIn total, 1005 children received QIV and 995 received control vaccine. Influenza A/B infection due to any circulating influenza strain occurred less frequently in children who received QIV versus children receiving a control vaccine. The absolute VE of QIV against any circulating influenza strain was 54% (95% confidence interval [CI]: 37%, 66%). The absolute VE of QIV against antigenically matching influenza strains was 68% (95% CI: 45%, 81%). Mean hemagglutination inhibition titers for all influenza strains in the QIV group increased post-vaccination, whereas increases were minimal in the control vaccine group; results from virus neutralization and neuraminidase-inhibition assays were generally consistent with the hemagglutination inhibition assay findings. Approximately 12 months after primary vaccination with QIV, antibody titers remained higher than pre-vaccination titers for most strains. In participants who were revaccinated, QIV elicited strong antibody responses. The overall safety profile and reactogenicity of QIV was comparable with control vaccine.ConclusionPrimary vaccination with QIV was well tolerated and effective in protecting children aged 6–35 months against influenza.