Increase In Geometric Mean Titer Research Articles

The safety and immunogenicity of vaccines administered to pregnant women living with HIV: a systematic review and meta-analysis

Human Immunodeficiency Virus (HIV)-exposed uninfected (HEU) infants have a higher burden of infectious diseases related morbidity and mortality compared with HIV-unexposed uninfected (HUU). Immunization of pregnant women living with HIV (PWLWH) could reduce the severity and burden of infectious diseases for HEU in early infancy. We conducted a systematic review of safety and immunogenicity of vaccines administered to PWLWH and meta-analyses to test the overall effect of immunogenicity comparing pregnant women without HIV (PWWH) to PWLWH. We searched MEDLINE, Embase, Web of Science, Virtual Health Library and Cochrane databases in accordance with PRISMA guidelines for randomized controlled trials and observational studies. Review articles, case series, conference abstracts, and animal studies were excluded. Studies were included from inception to 6th September 2023, with no language restrictions. Random effects meta-analyses were performed for immunogenicity using Review manager (RevMan) analysis software version 5.4.1, Geometric Mean Titer (GMT) values were transformed to obtain the mean and standard deviation within RevMan, the effect size was computed and reported as mean difference with respective 95% confidence intervals. The review was registered with PROSPERO CRD42021289081. We included 12 articles, comprising 3744 pregnant women, 1714 were PWLWH given either influenza, pneumococcal or an investigational Group B streptococcal (GBS) vaccine. Five studies described safety outcomes, and no increase in adverse events was reported in PWLWH compared to PWWH. The GMT increase from baseline to 28-35 weeks post vaccination in HA units ranged from 12.4 (95% CI: 9.84-14.9) to 238.8 (95% CI: 0.35-477.9). Meta-analyses of influenza vaccines showed the pooled geometric mean difference in Hemagglutination Inhibition (HAI) titers post vaccination was 56.01 (95% CI: 45.01-67.01), p<0.001. The increase was less in PWLWH when compared with PWWH:-141.76 (95% CI:-194.96,-88.55), p<0.001. There are limited data on the safety and immunogenicity of vaccines given to PWLWH making policy consideration in this group difficult when new vaccines are introduced. With new vaccines on the horizon, PWLWH need to be included in studies to promote vaccine confidence for this special population. This work was funded by Medical Research Council Joint Clinical Trials Round 9 [MR/T004983/1].

Safety and Preliminary Immunogenicity of Recombinant Hepatitis B (Bio Farma) Vaccine in Adults and Children: A Phase 1 Clinical Trial

Background: In order to fulfil the requirements of the national immunization program and sustain the production capacity of the monovalent Hepatitis B vaccine, this study aimed to assess the safety and immunogenicity of the recombinant Hepatitis B Vaccine (Bio Farma) using the new Hepatitis B bulk. Methods: This study was an experimental, randomized, double-blinded, and controlled Phase I clinical trial, with 100 healthy subjects divided into 50 adults and 50 adolescents. Subjects were randomly assigned to receive either the Bio Farma registered Recombinant Hepatitis B Vaccine (group A) or a new source of Hepatitis B bulk (group B). Subjects received one or three doses of vaccine, depending on the baseline anti-Hbs titer. Subjects were given diary cards to record solicited and unsolicited adverse events for 28 days following vaccination. Vaccine immunogenicity was assessed by measuring the level of HBsAg antibody titer elevation.Results: No serious adverse events were reported during clinical trials. The frequencies of adverse events were not significantly different between the two vaccine-randomized groups. The most immediately observed local reaction was local pain, reported by 35.7–42.8% of adults and 24.0–26.3% of adolescents, without any systemic reactions. Seroconversion in adults in group B reached 100% and 78.5% in group A, meanwhile in adolescent subjects in both groups it reached 100%. A substantial increase in geometric mean titer (GMT) was observed in the majority of subjects after immunization.Conclusion: Recombinant Hepatitis B Vaccine with a new source of HBsAg B bulk is safe, well tolerated, and highly immunogenic.

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients.

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.

Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus

IntroductionSeasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature.ObjectiveTo evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE.Methods24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated.ResultsJSLE patients and controls were comparable in current age [14.5 (10.1–18.3) vs. 14 (9–18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0–139.4) vs. 109.6 (95% CI 68.2–176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9–198.3) vs. 208.1 (150.5–287.8), p = 0.143] and factor increase in GMT [1.6 (1.2–2.1) vs. 1.9 (1.4–2.5), p = 0.574]. SLEDAI-2K scores [2 (0–17) vs. 2 (0–17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 (p = 0.713), as well as between patients with and without current use of prednisone (p = 0.420), azathioprine (p = 1.0), mycophenolate mofetil (p = 0.185), and methotrexate (p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups (p > 0.05).ConclusionThis is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. (www.clinicaltrials.gov, NCT03540823).

Robust immunogenicity to the H3N2 component of influenza A vaccine in primary Sjögren syndrome.

Influenza A (H3N2) virus is the major cause of morbidity/mortality due to seasonal influenza over 50years. Data about the safety/immunogenicity of influenza A/Singapore (H3N2) vaccine are scarce in primary Sjögren syndrome (pSS). Twenty-one consecutive pSS patients and 42 HC (healthy control individuals) were immunized with influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus. Rates of SP (seroprotection) and SC (seroconversion), GMT (geometric mean titers), FI-GMT (factor increase in GMT), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), and adverse events were appraised before and 4weeks post-vaccination. pSS and HC had similar mean age (51.2 ± 14.2 vs. 50.6 ± 12.1years, p = 0.886). Pre-vaccination SP rates were high in pSS and HC (90.5% vs. 71.4%, p = 0.114), and GMT were higher in pSS [80.0 (52.4-160.0) vs. 40.0 (20.0-80.0), p = 0.001]. The percentage of influenza vaccination in the preceding two years was elevated and similar in pSS and HC (94.1% vs. 94.6%, p = 1.000). GMT values augmented in both groups four weeks after vaccination and persisted higher in the first group [160.0 (80.0-320.0) vs. 80.0 (40.0-80.0), p < 0.001] with equivalent FI-GMT [1.4 (1.0-2.8) vs. 1.4 (1.0-2.0), p = 0.410]. Both groups had low and similar SC rates (19.0% vs. 9.5%, p = 0.423). ESSDAI values persisted steadily during the study (p = 0.313). No serious adverse events have occurred. The novel demonstration that the influenza A/Singapore (H3N2) vaccine induces a different pattern of immunogenicity from other influenza A constituents in pSS, featured by a desirable high pre- and post-vaccination immunogenicity, is in line with reported differences in immune responses between strains in trivalent vaccines and may be related to pre-existing immunity. gov: #NCT03540823. Key Points • This prospective study demonstrated a robust pre- and post-vaccination immunogenicity to influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus in primary Sjögren's syndrome (pSS). • This high immunogenicity pattern may be related to pre-existing immunization, or else it is related to immunogenicity differences of each strain. • This vaccine had an adequate safety profile in pSS, with no impact on disease activity.

Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine.

Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.

Antibody responses against heterologous H5N1 strains for an MF59-adjuvanted cell culture–derived H5N1 (aH5n1c) influenza vaccine in adults and older adults

ABSTRACT MF59-adjuvanted H5N1, cell culture-derived inactivated influenza vaccine (aH5N1c, AUDENZ®, Seqirus) is available for persons 6 months of age and older. During a pandemic, lack of preexisting immunity to novel influenza strains increases morbidity and mortality. This study examined the potential for an adjuvanted vaccine to provide cross-protection to novel viruses. Two similarly designed studies involving separate cohorts aged 18–64 and ≥65 y assessed immune responses to five heterologous H5N1 influenza strains elicited by two 7.5 μg doses of aH5N1c given 3 weeks apart. Geometric mean titers (GMT) on Days 1 and 43 and Day 43/Day 1 geometric mean ratios (GMRs) were determined with hemagglutination inhibition (HI) and microneutralization (MN). Rates of seroconversion (SC) and percentages of subjects with HI and MN ≥ 1:40 were determined. Significant increases in GMTs were observed on Day 43 after vaccination for all 5 heterologous strains in all ages tested. SC rates were 28–55% and 17–46% among those aged 18–64 and ≥65 y, respectively. MN ≥ 1:40 was observed in 38–100% of younger and 37–97% of older subjects, and HI ≥ 1:40 was achieved by 28–64% of subjects aged 18–64 y and by 17–57% of subjects aged ≥65 y. A SC rate ≥40% (97.5% CI) was met for two heterologous strains tested in adults aged 18–64 y. In adults aged 18–64 and ≥65 y, two 7.5 μg doses of aH5N1c demonstrated increased immunogenicity from baseline against five heterologous H5N1 strains, illustrating the potential for aH5N1c to provide cross-protection against other H5N1 strains.

Humoral Response to the Fourth BNT162b2 Vaccination and Link Between the Fourth Dose, Omicron Infection, and Disease Severity in Renal Transplant Recipients.

The effectiveness of the fourth BNT162b2 vaccination in reducing the rate and severity of coronavirus disease 2019 (COVID-19) caused by the Omicron variant in renal transplant recipients (RTRs) is unknown. Interviews were conducted with 447 RTRs regarding the status and timing of the fourth vaccination, prior vaccinations, and preceding COVID-19 infection. RTRs with polymerase chain reaction-confirmed COVID-19 infection from December 1, 2021, to the end of March 2022 were considered to have been infected with the Omicron variant and were interviewed to determine their disease severity. In a subgroup of 74 RTRs, the humoral response to the fourth dose was analyzed. In 30 RTRs, microneutralization assays were performed to reveal the humoral response to wild-type, Delta, and Omicron variant isolates before and after the fourth dose. Of 447 RTRs, 144 (32.2%) were infected with the Omicron variant, with 71 (49.3%) of the infected RTRs having received the fourth vaccine dose. RTRs who did not receive the fourth dose before the infection had more serious illness. In a subgroup of 74 RTRs, the fourth dose elicited a positive humoral response in 94.6% (70/74), with a significant increase in geometric mean titer for receptor-binding domain immunoglobulin G and neutralizing antibodies ( P < 0.001). The humoral responses to the Omicron variant before and after the fourth dose were significantly lower than the responses to the wild-type and the Delta variants. Overall, the fourth BNT162b2 dose was effective in reducing the rate and severity of Omicron disease in RTRs, despite the reduced humoral response to the variant.

BNT162b2 Third Booster Dose Significantly Increases the Humoral Response Assessed by Both RBD IgG and Neutralizing Antibodies in Renal Transplant Recipients.

Background: An impaired humoral response to full dose of BNT162b2 vaccine was observed in renal transplant recipients (RTR). Methods: To reveal predictors for humoral response to third vaccine, patients were stratified to positive (N = 85) and negative (N = 14) response groups based on receptor-binding domain (RBD) IgG ≥1.1 and neutralizing antibodies (NA) ≥ 16 dilution versus RBD IgG <1.1 or NA < 16, respectively. NA were detected using a SARS-CoV-2 pseudo-virus. Results: Response rate increased from 32.3% (32/99) before the third dose to 85.9% (85/99) post-third vaccine with a significant rise in geometric mean titers (GMTs) for RBD IgG and NA [0.79 (95% CI 0.65–0.96) vs. 3.08 (95% CI 2.76–3.45), p < 0.001 and 17.46 (95% CI 12.38–24.62) vs. 362.2 (95% CI 220.7–594.6), p < 0.001 respective. 80.6% (54/67) seroconverted and 96.9% (31/32) remained positive following the vaccine with a significant increase in GMTs for RBD IgG and NA. Age, ESRD secondary to diabetic nephropathy (DN) and renal allograft function were independent predictors for antibody response in RTR. Mycophenolic acid (MPA) use and dose had no impact on humoral response following the third booster. AEs were recorded for 70.1% of RTR population. Systemic AEs were more common in recipients with a positive humoral response as opposed to non-responders (45.2% versus 15.4% respectively, p = 0.04). Conclusion: 85.9% of RTR develop NA to BNT162b2 third vaccine, found effective in both negative and positive responders prior to the vaccine. Antigenic re-exposure overcame the suppressive effect of MPA on antibody response in RTR.

Antibody Response of BNT162b2 and CoronaVac Platforms in Recovered Individuals Previously Infected by COVID-19 against SARS-CoV-2 Wild Type and Delta Variant.

Vaccinating recovered patients previously infected by COVID-19 with mRNA vaccines to boost their immune response against wild-type viruses (WT), we aimed to investigate whether vaccine platform and time of vaccination affect immunogenicity against the SARS-CoV-2 WT and Delta variant (DV). Convalescent patients infected by COVID-19 were recruited and received one booster dose of the BNT162b2 (PC-B) or CoronaVac (PC-C) vaccines, while SARS-CoV-2 naïve subjects received two doses of the BNT162b2 (CN-B) or CoronaVac (CN-C) vaccines. The neutralizing antibody in sera against the WT and DV was determined with live virus neutralization assay (vMN). The vMN geometric mean titre (GMT) against WT in recovered individuals previously infected by COVID-19 reduced significantly from 60.0 (95% confidence interval (CI), 46.5–77.4) to 33.9 (95% CI, 26.3–43.7) at 6 months post recovery. In the PC-B group, the BNT162b2 vaccine enhanced antibody response against WT and DV, with 22.3-fold and 20.4-fold increases, respectively. The PC-C group also showed 1.8-fold and 2.2-fold increases for WT and DV, respectively, after receiving the CoronaVac vaccine. There was a 10.6-fold increase in GMT in the CN-B group and a 1.3-fold increase in the CN-C group against DV after full vaccination. In both the PC-B and PC-C groups, there was no difference between GMT against WT and DV after vaccination. Subjects in the CN-B and CN-C groups showed inferior GMT against DV compared with GMT against WT after vaccination. In this study, one booster shot effectively enhanced the pre-existing neutralizing activity against WT and DV in recovered subjects.

Influenza A/Singapore (H3N2) component vaccine in systemic lupus erythematosus: A distinct pattern of immunogenicity.

Influenza A (H3N2) virus is the most important cause of seasonal influenza morbidity and mortality in the last 50years, surpassing the impact of H1N1. Data assessing immunogenicity and safety of this virus component are lacking in systemic lupus erythematosus (SLE) and restricted to small reports with other H3N2 strains. This study aims to evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in SLE. 81 consecutive SLE patients and 81 age- and sex-matched healthy controls (HC) were vaccinated with the influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers(GMT), and factor increase in GMT(FI-GMT) and adverse events were assessed before and 4weeks post-vaccination. Disease activity and therapies were also evaluated. Before immunization, SLE and HC groups had high SP rates (89% vs 77%, p = 0.061) and elevated GMT titer with higher levels in SLE (129.1(104.1-154.1) vs 54.8(45.0-64.6), p < 0.001). Frequency of two previous years' influenza vaccination was high and comparable in SLE and HC (89% vs 90%, p = 1.000). Four weeks post-vaccination, median GMT increased for both groups and remained higher in SLE compared to HC (239.9(189.5-290.4) vs 94.5(72.6-116.4), p < 0.0001) with a comparable FI-GMT (2.3(1.8-2.9) vs 1.9(1.5-2.3), p = 0.051). SC rates were low and comparable for both groups (16% vs 11%, respectively, p = 0.974). Disease activity scores remained stable throughout the study (p = 1.000) and severe adverse events were not identified. Influenza A/Singapore (H3N2) vaccine has an adequate safety profile. The distinct immunogenicity pattern from other influenza A components characterized by a remarkably high pre- and post-vaccination SP rate and high GMT levels may be associated with previous influenza A vaccination. (www.clinicaltrials.gov, NCT03540823).

Safety and immunogenicity of a synthetic carbohydrate conjugate vaccine against Shigella flexneri 2a in healthy adult volunteers: a phase 1, dose-escalating, single-blind, randomised, placebo-controlled study

Shigella remains in the top four pathogens responsible for moderate to severe diarrhoea in children below 5 years of age. The shigella O-specific polysaccharide (O-SP) is a promising vaccine target. We developed a conjugate vaccine prototype incorporating a unique well defined synthetic oligosaccharide hapten, chemically designed for optimal antigenic, conformational, structural, and functional mimicry of the O-SP from Shigella flexneri 2a (SF2a). We aimed to assess the safety, tolerability, and immunogenicity of this original synthetic oligosaccharide-based vaccine candidate, SF2a-TT15, conceived to drive the antibody response towards the key protective determinants of the native lipopolysaccharide antigen, in a first-in-human phase 1 study. We did a first-in-human, dose-escalating, single-blind, observer-masked, randomised, placebo-controlled study at the Clinical Research Center of Tel Aviv Sourasky Medical Center (Israel). Participants were healthy adults aged 18-45 years with low titres of serum SF2a-specific IgG antibodies. 64 eligible participants were assigned to one of two cohorts. 32 participants in each of the two cohorts were randomly assigned via computer-generated algorithm in a stepwise manner to receive the 2 μg (cohort 1) and 10 μg oligosaccharide dose (cohort 2) of the SF2a-TT15 vaccine candidate non-adjuvanted or adjuvanted with aluminium hydroxide (alum) or matching placebos. The vaccine was administered as three single intramuscular injections into the arm, 28 days apart. The primary outcome was the incidence and severity of adverse events, which were assessed in the intention-to-treat safety population analysis including all participants who were randomly assigned and received at least one vaccine or placebo injection. The immunogenicity endpoints were secondary outcomes and were analysed in all participants who were randomly assigned, received all of the assigned injections before the time of the immunogenicity assessment, and provided blood samples for immunological follow-up (per-protocol immunogenicity analysis). The study is registered with ClinicalStudies.gov, NCT02797236 and is completed. Of 203 volunteers initially screened, 64 participants were enrolled between Sept 20, 2016, and Sept 26, 2017. In each of the two cohorts, 12 participants received the adjuvanted vaccine, 12 received the non-adjuvanted vaccine and eight received the matching placebo (four each). The SF2a-TT15 glycoconjugate was well tolerated at both doses. No serious or severe adverse events occurred. Overall, seven (88%) of eight to 12 (100%) of 12 in each group of volunteers had one adverse event or more after receiving the study agents with the majority of adverse events, 300 (98%) of 307, considered mild in intensity. Of the seven adverse events defined as moderate in severity, one (nausea) was suspected to be related to the vaccine candidate. At all post-immunisation days and for both oligosaccharide doses, whether adjuvanted or not, SF2a-TT15 induced significantly higher serum IgG anti-SF2a lipopolysaccharide geometric mean titres (GMTs) as compared with baseline or with the corresponding GMTs in placebo recipients (p<0·01). After one injection, the non-adjuvanted 10 μg oligosaccharide dose induced a 27-times increase in IgG GMT (5080 vs 189) and the non-adjuvanted 2 μg oligosaccharide dose induced a five-times increase (1411 vs 283), compared with baseline. Alum enhanced the specific IgG response at 2 μg oligosaccharide dose after the third injection (GMTs 3200 vs 1176, p=0.045). SF2a-TT15 was safe and well tolerated and induced high titres of anti-SF2a LPS IgG antibodies. These results support further evaluation of this original synthetic oligosaccharide-protein conjugate vaccine candidate for safety, immunogenicity, and protective efficacy in target populations. The European Union Seventh Framework Programme.

Influenza vaccination in breast cancer patients during subcutaneous trastuzumab in adjuvant setting

BackgroundDespite the current recommendation for influenza vaccination in cancer patients with active oncological therapy, limited data are available on the efficacy of vaccination in cancer patients receiving targeted therapies. We aimed to investigate the immunogenicity and tolerability of influenza vaccination in breast cancer patients treated with trastuzumab in adjuvant setting.MethodsA prospective open-label multicenter study was performed including patients with breast cancer during trastuzumab treatment in adjuvant setting and healthy controls. Blood samples were taken before, 4 weeks after, and 12 weeks after a single dose of trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Hongkong4801/2014 (H3N2), and B/Brisbane/60/2008. Levels of serum antibody titers to hemagglutinin for H1N1 and influenza B strains were measured.ResultsTwenty breast cancer patients and 37 controls were included in the study. No difference in seroprotection rate between trastuzumab-treated patients and controls was observed for either H1N1 (100% in both groups) or B strain (78.9% vs. 89.2%, p value = 0.423). A statistically significant increase in geometric mean titers from baseline was seen in both groups and was evident both 4 weeks and 12 weeks after vaccination. Adverse events in the trastuzumab-treated group were uncommon and mild with only one serious adverse event not related to vaccination.ConclusionBreast cancer patients treated with trastuzumab in adjuvant setting seem to benefit from influenza vaccination in terms of immunogenicity without increasing the risk for adverse events. The current data support the recommendation to offer influenza vaccination in breast cancer patients treated with this type of targeted therapy.

Evervac: phase I/II study of immunogenicity and safety of a new adjuvant-free TBE vaccine cultivated in Vero cell culture

ABSTRACT Approximately 10,000 cases of tick-borne encephalitis (TBE), a serious disease of the central nervous system caused by tick-borne encephalitis virus (TBEV), are registered worldwide every year. Vaccination against TBE remains the most essential measure of preventing the disease. Unlike available TBE vaccines, a new inactivated lyophilized candidate vaccine Evervac is produced in Vero continuous cell culture and its final formulation does not include aluminum-based adjuvants. To study the safety and immunogenicity of Evervac, healthy adults 18–60 y of age were immunized twice at 30-d intervals. The study was single-blind, randomized, comparative, controlled, and was conducted in TBE-endemic areas. The commercial lyophilized vaccine TBE-Moscow was used as a comparison treatment. The subjects were observed for incidence, severity, and duration of adverse reactions. It was shown that the severity of local and systemic reactions in the Evervac vaccine group was mild to moderate. There were no significant differences in the incidence of adverse reactions between the Evervac and TBE-Moscow vaccine groups. Immunization with Evervac produced a significant increase in geometric mean titer (GMT) of anti-TBEV antibodies in both initially seronegative and seropositive recipients. The seroconversion rate for the initially seronegative recipients was 69% (GMT = 1:214) after the first dose and reached 100% after the second dose. In these parameters, there were no significant differences between the study and control vaccine groups. Thus, the adjuvant-free Vero-based vaccine Evervac was well tolerated, had low reactogenicity, induced a pronounced immune response, and was overall non-inferior to the commercial adjuvanted TBE vaccine used as a control.

Heterotypic Neuraminidase Antibodies Against Different A(H1N1) Strains are Elicited after Seasonal Influenza Vaccination.

Neuraminidase (NA) content is not standardized in current seasonal influenza vaccines; neither anti-NA antibodies (anti-NA Abs) are measured nor is it well-defined as a correlate of humoral protection. In this work, the presence of NA1 antibodies against classical A(H1N1) and A(H1N1) pdm09 subtypes was studied before and after vaccination with seasonal vaccines containing A/California/07/2009 strain (A(H1N1) pdm09 subtype). By Enzyme-Linked Lectin Assay (ELLA; Consortium for the Standardization of Influenza Seroepidemiology), we analyzed serum samples from two different cohorts (adults and elderly). The presence of anti-NA Abs at titers ≥1/40 against classical A(H1N1) and A(H1N1) pdm09 subtypes were frequently found in both age groups, in 81.3% and 96.3% of adults and elderly, respectively. The higher titers of anti-NA Abs (NAI titers) were detected more frequently against classical A(H1N1) strains according to the expected age when the first flu infection takes place. In this way, an Original Antigenic Sin phenomenon related to NA seems to be part of the immune response against flu. Seasonal-vaccination induced homologous seroconversion against NA of A(H1N1) pdm09 subtype in 52.5% and 55.0%, and increased the Geometric Mean Titers (GMTs) in 70.0% and 78.8% of adults and elderly, respectively. Seasonal vaccination also induced a heterotypic anti-NA Abs response against classical A(H1N1) strains (seroconversion at least in 8.8% and 11.3% of adults and elderly, respectively, and an increase in GMTs of at least 28.0% in both age groups). These anti-NA Abs responses occur even though the seasonal vaccine does not contain a standardized amount of NA. This work demonstrates that seasonal vaccines containing the A(H1N1) pdm09 subtype induce a broad antibody response against NA1, that may be a target for future influenza vaccines. Our study is one of the first to analyze the presence of Abs against NA and the response mediated by NAI titers after seasonal influenza vaccination.

Neutralization and hemagglutination-inhibition antibodies following influenza vaccination of HIV-infected and HIV-uninfected pregnant women

BackgroundWe previously reported that despite HIV-infected pregnant women had modest humoral immune responses to inactivated influenza vaccine (IIV) measured by hemagglutination-inhibition (HAI) assay, the observed vaccine efficacy against influenza disease was higher than predicted by HAI; suggesting that IIV may confer protection to HIV-infected individuals by additional mechanisms. We evaluated the response to IIV by microneutralization (MN) and HAI assays and correlated both methods in HIV-infected and HIV-uninfected pregnant women.MethodsMN and HAI antibodies were measured pre-vaccination and approximately one-month post-vaccination in 80 HIV-infected and 75 HIV-uninfected women who received IIV. Geometric mean titers (GMTs), fold-change in titers and seroconversion rates were determined for the three influenza stains in the vaccine.ResultsAfter vaccination there were significant increases in MN and HAI GMTs for the three vaccine strains in both HIV-infected and HIV-uninfected women. HIV-infected women had, however, a lower immune response compared to HIV-uninfected. Fold-increases were 2 to 3-times higher for MN assay compared to HAI assay for the influenza-A strains. Also a higher percentage of women seroconverted by MN than by HAI assay for the influenza-A strains. There was high positive correlation between MN and HAI assays, except for the B/Victoria strain at pre-vaccination.ConclusionsIn general, the MN assay was more sensitive than the HAI assay. Microneutralization antibodies might correlate better with protection against influenza infection.

A randomized, blinded, placebo-controlled trial comparing antibody responses to homeopathic and conventional vaccines in university students

BackgroundHomeopathic vaccines are licensed in many countries but scientific data to support their use are sparse. The goal of this study was to compare the antibody response of homeopathic and conventional vaccines and placebo in young adults. We hypothesized that there would be no significant difference between homeopathic vaccines and placebo, while there would be a significant increase in antibodies in those received conventional vaccines. MethodsA randomized blinded placebo-controlled trial was conducted where 150 university students who had received childhood vaccinations were assigned to diphtheria, pertussis, tetanus, mumps, measles homeopathic vaccine, placebo, or conventional diphtheria, pertussis, tetanus (Tdap) and mumps, measles, rubella (MMR) vaccines. The primary outcome was a ≥ two-fold increase in antibodies from baseline following vaccination as measured by ELISA. Participants, investigators, study coordinator, data blood drawers, laboratory technician, and data analyst were blinded. ResultsNone of the participants in either the homeopathic vaccine or the placebo group showed a ≥ two-fold response to any of the antigens. In contrast, of those vaccinated with Tdap, 68% (33/48) had a ≥ two-fold response to diphtheria, 83% (40/48) to pertussis toxoid, 88% (42/48) to tetanus, and 35% (17/48) of those vaccinated with MMR had a response to measles or mumps antigens (p < 0.001 for each comparison of conventional vaccine to homeopathic vaccine or to placebo). There was a significant increase in geometric mean titres of antibody from baseline for conventional vaccine antigens (p < 0.001 for each), but none for the response to homeopathic antigens or placebo. ConclusionsHomeopathic vaccines do not evoke antibody responses and produce a response that is similar to placebo. In contrast, conventional vaccines provide a robust antibody response in the majority of those vaccinated.Trial Registry:NCT 02825368.

Immunogenicity of the CYD tetravalent dengue vaccine using an accelerated schedule: randomised phase II study in US adults

BackgroundThe live attenuated tetravalent dengue vaccine (CYD-TDV) is licensed using a 0-, 6- and 12-month schedule in dengue-endemic areas. An effective shorter schedule may provide more rapid, optimal protection of targeted populations during vaccine campaigns in dengue-endemic countries. We compared immune responses to two schedules of CYD-TDV in a non-endemic population. We also evaluated the impact of yellow fever (YF) co-administration.MethodsThis phase II, open-label, multicentre study enrolled 390 healthy 18–45-year-olds in the USA with no prior exposure to dengue. Participants were randomised (4:4:4:1) to four treatment groups stratified by prior YF vaccine status: Group 1, CYD-TDV standard 0–6–12 months schedule; Group 2, CYD-TDV accelerated 0–2–6 months schedule; Group 3, CYD-TDV accelerated schedule with YF co-administered (dose 1); Group 4, YF vaccination only. Neutralising antibody geometric mean titres (GMTs) and percentages of seropositive participants (antibody titres ≥10 [1/dil]) were measured against each dengue serotype using a 50% plaque reduction neutralisation test.ResultsOn D28 post-CYD-TDV dose 3, there were no marked differences in seropositivity rates and GMTs between Groups 1 and 2. In Groups 1 and 2 respectively, 73.4 and 82.4% were dengue seropositive for ≥3 serotypes, with 50.0 and 42.6% seropositive against all four serotypes. Flavivirus status (FV+ or FV−) at baseline did not markedly affect GMTs and seropositivity rates with either schedule. In Groups 1 and 2, GMTs measured 6 months after the third dose decreased against all serotypes, except for a small increase in GMT for serotype 4 in Group 1. In addition, dengue seropositivity remained above 70% for serotypes 2, 3 and 4 in Groups 1 and 2. Co-administration with YF did not affect antibody responses against dengue and YF or impact vaccine safety following completion of the compressed schedule, compared to dengue or YF vaccination alone.ConclusionsThe live attenuated CYD-TDV vaccine given in a compressed schedule in a non-endemic setting can elicit similar antibody responses to the licensed CYD-TDV schedule.Trial registrationThis trial was registered on cinicaltrials.gov, NCT01488890 (December 8, 2011).

Antibody Persistence up to 3 Years After Primary Immunization With Inactivated Japanese Encephalitis Vaccine IXIARO in Philippine Children and Effect of a Booster Dose.

An inactivated Vero cell culture derived Japanese encephalitis virus vaccine (IXIARO) requires a booster dose 1 year after primary schedule for long-term antibody persistence in adults. The aim of this study is to evaluate immunogenicity and safety of a booster dose in children 2 months to <18 years of age. This is a randomized, controlled open-label study in the Philippines. Three hundred children vaccinated with IXIARO in a previous trial were randomized 1:1 to receive either no booster or a booster 12 months after initiation of the primary series. Neutralizing antibody titers were assessed before and after the booster and up to 3 years after primary series. Safety endpoints included the rate of subjects with solicited adverse events (AEs), unsolicited AEs and serious AEs within 1 month after the booster. Geometric mean titer declined by 1 year after the primary series, but titers remained above the established protective threshold in 85%-100% of children depending on age group. The booster led to a pronounced increase in geometric mean titer and 100% seroprotection rate in all age groups. The booster was well tolerated, with AE rates lower compared with the primary series. Most AEs were mild. A booster dose of IXIARO administered 12 months after the primary immunization was well tolerated and highly immunogenic.

Immunogenicity of trivalent influenza vaccines in patients with chronic kidney disease undergoing hemodialysis: MF59-adjuvanted versus non-adjuvanted vaccines

ABSTRACTBackgrounds: Patients with chronic kidney disease (CKD) are at an increased risk of morbidity and mortality from influenza. However, the immunogenicity of influenza vaccine is known to be attenuated in these patients. In this study, the immunogenicity of MF59-adjuvanted and non-adjuvanted trivalent influenza vaccines was compared in CKD patients undergoing hemodialysis (HD).Methods: During 2013–2014, 179 CKD patients undergoing HD participated in the study. The patients were randomized into either MF59-adjuvanted vaccine group or non-adjuvanted vaccine group and were immunized with the respective vaccine. Sera were collected prior to vaccination and at 1 month (88 patients in MF59-adjuvanted vaccine group and 86 patients in non-adjuvanted vaccine group) and 6 months post vaccination. Levels of hemagglutination inhibition antibodies were measured.Results: The seroconversion rate of all 3 vaccine strains at 1 month post-vaccination was significantly higher in the MF59-adjuvanted group than in the non-adjuvanted group (47.7% vs. 17.4%, A/H1N1; 42.0% vs. 16.3%, A/H3N2; 31.8% vs. 7.0%, B, P < 0.01). One month post-vaccination, the fold increase in geometric mean titer from pre-vaccination for A/H1N1, A/H3N2 and B viruses was significantly greater in the MF59-adjuvanted group than in the non-adjuvanted group. In elderly patients (≥65 years), the seroconversion rate at 1 month post-vaccination against influenza B strain was higher in the MF59-adjuvanted group than in the non-adjuvanted group (33.3% vs. 7.1%, P = 0.03).Conclusion: The MF59-adjuvanted influenza vaccine showed better immunogenicity than the non-adjuvanted influenza vaccine in CKD patients undergoing HD.