Decline In Antibody Titers Research Articles

Waning of Anti-spike Antibodies in AZD1222 (ChAdOx1) Vaccinated Healthcare Providers: A Prospective Longitudinal Study.

IntroductionCoronavirus disease 2019 (COVID-19) vaccines are nothing short of a miracle story halting the pandemic across the globe. Nearly half of the global population has received at least one dose. Nevertheless, antibody levels in vaccinated people have shown waning, and breakthrough infections have occurred. Our study aims to measure antibody kinetics following AZD1222 (ChAdOx1) vaccination six months after the second dose and the factors affecting the kinetics.Materials and methodsWe conducted a prospective longitudinal study monitoring for six months after the second of two AZD1222 (ChAdOx1) vaccine doses in healthcare professionals and healthcare facility employees at Veer Surendra Sai Institute of Medical Sciences and Research (included doctors, nurses, paramedical staff, security and sanitary workers, and students). Two 0.5-mL doses of the vaccine were administered intramuscularly, containing 5 x 1010 viral particles 28 to 30 days between doses. We collected blood samples one month after the first dose (Round 1), one month after the second dose (Round 2), and six months after the second dose (Round 3). We tested for immunoglobulin G (IgG) levels against the receptor-binding domain of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by chemiluminescence microparticle immunoassay. We conducted a linear mixed model analysis to study the antibody kinetics and influencing factors.ResultsOur study included 122 participants (mean age, 41.5 years; 66 men, 56 women). The geometric mean IgG titers were 138.01 binding antibody units (BAU)/mL in Round 1, 176.48 BAU/mL in Round 2, and 112.95 BAU/mL in Round 3. Seven participants showed seroreversion, and 11 had breakthrough infections. Eighty-six participants showed a substantial decline in antibody titer from Rounds 2 to 3. Persons aged 45 or older had higher mean titer than people aged younger than 45 years. Overweight and obese (BMI ≥ 25 kg/m2) had a higher mean titer than average or underweight persons. The only significant predictor of IgG titers at six months was SARS-CoV-2 infection on mixed model analysis.ConclusionWe found a substantial decline in antibody levels leading to seven cases of seroreversion in healthcare professionals who received the ChAdOx1 vaccine. History of prior COVID-19 was the only significant factor in antibody levels at six months. Seroreversion and breakthrough infection warrant further research into the optimal timing and potential benefits of booster doses of the AZD1222 (ChAdOx1) COVID-19 vaccine.

Kinetics of Anti-Sars-Cov-2 Antibody Responses 3 Months Post Complete Vaccination with BNT162b2; A Prospective Study in 283 Health Workers

Background: Levels of neutralizing antibodies (NΑbs) against SARS-CoV-2 correlate with clinically relevant immune protection from COVID-19. However, a slight decline in antibody titers has become evident even at one month following the second BNT162b2 shot, whereas increased time since the second vaccine dose has been associated with decreased NAb activity against SARS-CoV-2 variants. The aim of this study was to investigate the kinetics of NAbs and anti-S-RBD IgGs after vaccination of health workers with the BNT162b2 mRNA vaccine over a period of up to three months after the second shot. The possible influence of comorbidities, characteristics of the subjects, co-medication, and adverse events was also investigated.Methods: All participants have been enrolled in a large prospective study (NCT04743388) evaluating the kinetics of anti-SARS-CoV-2 antibodies after COVID-19 vaccination. Main inclusion criteria for participation in this study were eligibility for vaccination according to the national program for COVID-19, age above 18 years, and ability to sign the informed consent form. Major exclusion criteria included the presence of active malignant disease, immunosuppressive therapy, and end-stage renal disease. According to National Immunization Program, access to the BNT162b2 mRNA vaccine was available to anyone 18 years of age or older.NΑbs and anti-S-RBD IgG titers were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111), using FDA approved methods, namely, cPass™ SARS-CoV2 NAbs Detection Kit (GenScript, Piscataway, NJ, USA) and Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH, Mannheim, Germany), respectively.Results: In total, 283 health workers (median age 48 years) were included in this study. On D1, immediately before vaccination, the median neutralizing inhibition was 14.2%, while 29 individuals (10.2%) had inhibition levels above the positive threshold of the method (30%). NAbs showed a rapid increase from D8 to D36 on a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50 a slight decrease in NAbs values was detected and it became more prominent between D50 and D111, when the rate of decline was determined at -0.11 per day. The median (SD) NAbs titers at D111 were 92.7% (11.8). Paired grouped comparisons using the Wilcoxon signed ranks test showed statistically significant differences in inhibition levels between pairs: D36 vs. D50, D36 vs. D111, and D50 vs. D111 (for all three comparisons p<0.001) (Figure A).A similar pattern was also observed for anti-S-RBD antibodies. It is worth mentioning that compared to NAbs, the maximum anti-S-RBD levels were reached two weeks later, i.e., at D36. Interestingly, anti-S-RBDs showed a steeper increase during D22-D36 and a lower decline rate during D36-D111. All consecutive pairs comparison, using Wilcoxon's test, led to p-values<0.001 (Figure B).There was an almost linear relationship between NAbs and anti-S-RBD at D22 (Spearman's rho correlation coefficient equal to 0.718). However, their relationship became non-linear from D36; this is due to the steep increase in anti-S-RBD levels that was observed during the D22-D36 period, while the corresponding increase rate for NAbs was much lower. Also, the decline of anti-S-RBD titers was lower compared to that of NAbs. The composite effect of these functions led to a non-linear pattern.Furthermore, prior COVID-19 and younger age were associated with superior antibody responses over time. Regarding those with previous positive PCR for SARS-CoV-2, significantly higher levels were observed at the initial phase (D1, D8) (Mann-Whitney p-values<0.001) and at D111 (p=0.046). From D50 there was a trend for a slower decline rate for those with previous positive PCR. Younger individuals had higher antibody titers at D36, D50, and D111, which is due to a slower decline in NAbs compared to the older group of participants (for all three comparisons, Wilcoxon's p-values were<0.05).Conclusions: We found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals. Our longitudinal study is ongoing to determine the time point of NAbs reduction below the positivity threshold; then a booster vaccine dose might be necessary to maintain humoral immunity against SARS-CoV-2. [Display omitted] DisclosuresTerpos: Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; BMS: Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding. Gavriatopoulou: Janssen: Honoraria; Karyopharm: Honoraria; Genesis: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Dimopoulos: Takeda: Honoraria; Beigene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria.

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

BackgroundChagas disease remains a significant public health problem in Latin America. There are only two chemotherapy drugs, nifurtimox and benznidazole, and both may have severe side effects. After complete chemotherapy of acute cases, seropositive diagnosis may revert to negative. However, there are no definitive parasitological or serological biomarkers of cure.MethodsFollowing a pilot study with seven Bolivian migrants to Spain, we tested 71 serum samples from chronic patients (mean age 12.6 years) inhabiting the Argentine Chaco region. Benznidazole chemotherapy (5–8 mg/kg day, twice daily for 60 days) was administered during 2011–2016. Subsequently, pre-and post-chemotherapy serum samples were analysed in pairs by IgG1 and IgG ELISA using two different antigens and Chagas Sero K-SeT rapid diagnostic tests (RDT). Molecular diagnosis by kDNA-PCR was applied to post-treatment samples.ResultsPilot data demonstrated IgG1 antibody decline in three of seven patients from Bolivia 1 year post-treatment. All Argentine patients in 2017 (averaging 5 years post-treatment), except one, were positive by conventional serology. All were kDNA-PCR-negative. Most (91.5%) pre-treatment samples were positive by the Chagas Sero K-SeT RDT, confirming the predominance of TcII/V/VI. IgG1 and IgG of Argentine patients showed significant decline in antibody titres post-chemotherapy, with either lysate (IgG, P = 0.0001, IgG1, P = 0.0001) or TcII/V/VI peptide antigen (IgG, P = 0.0001, IgG1, P = 0.0001). IgG1 decline was more discriminative than IgG. Antibody decline after treatment was also detected by the RDT. Incomplete treatment was associated with high IgG1 post-treatment titres against lysate (P = 0.013), as were IgG post-treatment titres to TcII/V/VI peptide (P = 0.0001). High pre-treatment IgG1 with lysate was associated with Qom ethnicity (P = 0.045). No associations were found between gender, age, body mass index and pre- or post-treatment antibody titres.ConclusionsWe show that following chemotherapy of early chronic Chagas disease, significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure.Graphical abstractWe show that following chemotherapy of early chronic Chagas disease, a significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure.

Immunization Coverage and Antibody Retention against Rabies in Domestic Dogs in Lusaka District, Zambia.

Rabies remains endemic in Zambia. Despite conducting canine vaccinations in Lusaka district, the vaccination coverage and actual seropositivity in the dog population in Lusaka district are rarely evaluated. This study estimated the seropositivity-based immunization coverage in the owned dog population in Lusaka district using the expanded program on immunization cluster survey method. The time-series trend of neutralizing antibodies against rabies in vaccinated dogs was also evaluated. Of 366 dogs in 200 dog-owning households in Lusaka district, blood samples were collected successfully from 251 dogs. In the sampled dogs, 42.2% (106/251) had an antibody titer ≥0.5 IU/mL. When the 115 dogs whose blood was not collected were assumed to be seronegative, the minimum immunization coverage in Lusaka district’s owned dog population was estimated at 29.0% (95% confidence interval: 22.4–35.5). It was also found that a single vaccination with certified vaccines is capable of inducing protective levels of antibodies. In contrast, higher antibody titers were observed in multiple-vaccinated dogs than in single-vaccinated dogs, coupled with the observation of a decline in antibody titer over time. These results suggest the importance of continuous booster immunization to maintain herd immunity and provide useful information to plan mass vaccination against rabies in Zambia.

High-throughput quantitation of SARS-CoV-2 antibodies in a single-dilution homogeneous assay

SARS-CoV-2 emerged in late 2019 and has since spread around the world, causing a pandemic of the respiratory disease COVID-19. Detecting antibodies against the virus is an essential tool for tracking infections and developing vaccines. Such tests, primarily utilizing the enzyme-linked immunosorbent assay (ELISA) principle, can be either qualitative (reporting positive/negative results) or quantitative (reporting a value representing the quantity of specific antibodies). Quantitation is vital for determining stability or decline of antibody titers in convalescence, efficacy of different vaccination regimens, and detection of asymptomatic infections. Quantitation typically requires two-step ELISA testing, in which samples are first screened in a qualitative assay and positive samples are subsequently analyzed as a dilution series. To overcome the throughput limitations of this approach, we developed a simpler and faster system that is highly automatable and achieves quantitation in a single-dilution screening format with sensitivity and specificity comparable to those of ELISA.

Kinetics of anti-SARS-CoV-2 antibodies over time. Results of 10 month follow up in over 300 seropositive Health Care Workers

BackgroundThe kinetics of the antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated since long-term duration of antibody remains largely unknown, particularly in infected healthcare workers (HCW). MethodsProspective study, evaluating the longitudinal profile of anti-SARS-CoV-2 antibody titers in a random sample of 331 seropositive healthcare workers (HCW) of Spanish Hospitals Group. Serial measurements of serum IgG-anti-SARS-CoV-2 were obtained at baseline (April-May,2020), and in 2 follow-up visits. Linear mixed models were used to investigate antibody kinetics and associated factors. ResultsA total of 306 seropositive subjects (median age: 44.7years;69.9% female) were included in the final analysis. After a median follow-up of 274 days between baseline and final measurement, 235(76.8%) maintained seropositivity. Antibody titers decreased in 82.0%, while remained stable in 13.1%. Factors associated with stability of antibodies over time included age≥45 years, higher baseline titers, severe/moderate infection and high-grade exposure to COVID-19 patients. In declining profile, estimated mean antibody half-life was 146.3 days(95%CI:138.6–154.9) from baseline. Multivariate models show independent longer durability of antibodies in HCW with high-risk exposure to COVID-19 patients (+14.1 days;95%CI:0.6–40.2) and with symptomatic COVID-19 (+14.1 days;95%CI:0.9–43.0). The estimated mean time to loss antibodies was 375(95% CI:342–408) days from baseline. ConclusionsWe present the first study measuring the kinetics of antibody response against SARS-CoV-2 in HCW beyond 6 months. Most participants remained seropositive after 9 months but presented a significant decline in antibody-titers. Two distinct antibody dynamic profiles were observed (declining vs. stable). Independent factors associated with longer durability of antibodies were symptomatic infection and higher exposure to COVID-19 patients.

Association between self-reported signs and symptoms and SARS-CoV-2 antibody detection in UK key workers

BackgroundScreening for SARS-CoV-2 antibodies is under way in some key worker groups; how this adds to self-reported COVID-19 illness is unclear. In this study, we investigate the association between self-reported belief of COVID-19 illness and seropositivity. MethodsCross-sectional study of three key worker streams comprising (A) Police and Fire & Rescue (2 sites) (B) healthcare workers (1 site) and (C) healthcare workers with previously positive PCR result (5 sites). We collected self-reported signs and symptoms of COVID-19 and compared this with serology results from two SARS-CoV-2 immunoassays (Roche Elecsys® and EUROIMMUN). ResultsBetween 01 and 26 June, we recruited 2847 individuals (Stream A: 1,247, Stream B: 1,546 and Stream C: 154). Amongst those without previous positive PCR tests, 687/2,579 (26%) reported belief they had COVID-19, having experienced compatible symptoms; however, only 208 (30.3%) of these were seropositive on both immunoassays. Both immunoassays had high sensitivities relative to previous PCR positivity (>93%); there was also limited decline in antibody titres up to 110 days post symptom onset. Symptomatic but seronegative individuals had differing symptom profiles and shorter illnesses than seropositive individuals. ConclusionNon-COVID-19 respiratory illness may have been mistaken for COVID-19 during the outbreak; laboratory testing is more specific than self-reported key worker beliefs in ascertaining past COVID-19 disease.

SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn

As COVID vaccines roll out, internists and other health care providers are being turned to as trusted sources of information for patients and communities. Here, experts from NIAID outline the current state of knowledge regarding such vaccines. They contrast vaccine platforms, summarize clinical trial data regarding efficacy and safety, and comment on key questions including the ability of current vaccines to protect against infection and to decrease the prevalence of virus in the community.

Evolution of Antibody Titers Up to 6 Months Post-Immunization With the BNT162b2 Pfizer/BioNTech Vaccine in Greece

Background: Despite accumulating evidence of the durable effectiveness of the BNT162b2 mRNA Covid-19 vaccine over time, there is a lack of phase IV studies reporting data on long-term vaccine-induced immunogenicity in specific population groups like healthcare workers. The aim of the present study was to comprehensively assess the 6-month course of humoral immune responses elicited by the BNT162b2 vaccine among healthcare workers in Greece.Methods: We employed theSARS-CoV-2 IgG II Quant assay on the Architect Systemto longitudinally assess titers of neutralizing IgG against the receptor-binding domain of the S1 subunit of the spike protein in participant-derived serum samples.Results: Our study encompassed 252 participants whose anti-RBD IgG titers were monitored through the course of six months. The overall IgG GMC almost doubled compared to its value 14 days after the first dose (fold change=1.954) yet declined by 94% compared to its levels 14 days after the second dose (fold change =0.061) and by 66% compared to its 3-month value (fold change =0.335). However, in 99% of our sample antibody titers exceeded the seropositivity threshold of 50 AU/ml. A substantial discrepancy in antibody levels was observed upon history of infection (p-valueFurther statistical modeling revealed that in subjects aged under 60, antibody titers marked a decline from 10000 to 1000 (from 4 to 3 in the log10 scale) within 6 months’ time, whereas the same effect was observed in 4 months among vaccinated individuals aged over 60. Prognostic results obtained from the modeling procedure suggest that subjects with a positive history of infection that received both doses of the vaccine will probably notice such a drop in their antibody titers well beyond one-year post-immunizationCompared to antibody levels post-2nd dose, males and uninfected subjects marked a greater 6-month decline than their counterparts, while age did not seem to affect antibody trends within that time span. Lastly, the drop of antibody titers observed from 3 to 6 months post-immunization was homogenous in both genders and age groups, only varying upon history of infection. Conclusion: Our findings are highly indicative of the durable antibody responses generated by the BNT162b2 vaccine in all age groups, while highlighting the significantly slower decline of antibody titers in the previously infected. This evidence suggests that the long-term antibody trajectories observed in the seropositive group are potentially equivalent to the benefit of a third dose given to the uninfected, safeguarding the longevity of their humoral immunity over time.

Combined usage of rHVT-H5 and Re-6 vaccines towards an effective avian influenza vaccination program for commercial layer chickens

Vaccination against highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 is one of the possible means to protect chickens against its outbreak in endemic countries. Early vaccination of layer birds with recombinant vector vaccine based on turkey herpesvirus expressing H5 gene (rHVT-H5) provides longer protection while inactivated vaccine Re-6 needs multiple booster doses to achieve continuous antibody titer. Therefore, this study was carried out to offer a vaccination program using live rHVT-H5 and inactivated Re-6 vaccines in field condition. For this trial, five ISA brown commercial layer chicken farms were raised with 500 birds per farm. Two licensed vaccines- rHVT-H5 and Re-6 in Bangladesh were used for this trial where birds in farms 1 and 2 were administered only rHVT-H5 vaccine at one-day-old, and farms 3 and 4 rHVT-H5 vaccine at one-day-old then boosted with Re-6 vaccine at 25 weeks of age. Farm 5 was not vaccinated and functioned as control. Blood samples were randomly collected from 20 birds in each farm at 3-week interval from 2 weeks old till 65 weeks and harvested serum analyzed by haemagglutination inhibition (HI) test for antibodies against HPAIV H5N1. The titer of haemagglutination inhibiting antibodies against AIV H5N1 on farms 3 and 4 was considerably high and remained up to 65 weeks. However, in farm 1 and 2 there was decline in antibody titer after 56 weeks of age. This study demonstrated that the combined use of rHVT-H5 vaccine at one-day-old and Re-6 at 25 weeks of age enhanced a longer lasting protective antibody against circulating HPAIV H5N1 in commercial layer chickens in Bangladesh.&#x0D; Stamford Journal of Microbiology, Vol.10 (1) 2020: 9-11

Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers.

Although antibody response to SARS-CoV-2 can be detected early during the infection, several outstanding questions remain to be addressed regarding the magnitude and persistence of antibody titer against different viral proteins and their correlation with the strength of the immune response. An ELISA assay has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length Nucleocapsid protein (N). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies as well as soluble pro-inflammatory mediators in the sera. Non-hospitalized subjects showed lower antibody titers and blood pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested. Noteworthy, in non-severe COVID-19 infections, antibody titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Thus, rapid decline in antibody titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection, suggesting that antibody-mediated protection against re-infection with SARS-CoV-2 is of short duration. These results suggest caution in using serological testing to estimate the prevalence of SARS-CoV-2 infection in the general population.

One-Year Decline of Poliovirus Antibodies Following Fractional-Dose Inactivated Poliovirus Vaccine.

Fractional dose (one-fifth of full intramuscular dose) of inactivated poliovirus vaccine (fIPV) administered intradermally is used as IPV dose-sparing strategy. We compared the rate of decline of poliovirus antibodies (PVA) in recipients of 2 doses of fIPV or IPV. A community-based randomized controlled trial was conducted in Karachi, Pakistan. Children aged 14 weeks were randomized into fIPV or full IPV (study arms A, B) and received 1 vaccine dose at age 14 weeks and 1 at age 9 months. PVAs were measured at age 14, 18 weeks and 10, 21 months. Seroprevalence of poliovirus type 2 antibodies in 170/250 (68%) children after 2 IPV or fIPV doses at age 10 months in A and B reached 100% vs 99% (P = .339), and at 21 months, 86% vs 67% (P = .004). Between age 10 and 21 months antibody log2 titers dropped from ≥ 10.5 to 6.8 in A and from 9.2 to 3.7 in B. There was a significant decline in antibody titers 12 months following the second IPV dose. The slope of decline was similar for full IPV and fIPV recipients. The results provide further evidence that fIPV is a viable option for IPV dose-sparing. NCT03286803.

Response of Sport Horses to Different Formulations of Equine Influenza Vaccine.

The international governing body of equestrian sports requires that horses be vaccinated against equine influenza within 6 months and 21 days of competing. The aim of this study was to compare the antibody response of young sport horses to six-monthly booster vaccination with equine influenza vaccines of different formulations. An inactivated vaccine was allocated to 35 horses and subunit and recombinant vaccines were allocated to 34 horses each. After vaccination, all horses were monitored for evidence of adverse reactions. Whole blood samples were collected at the time of vaccination and on nine occasions up to six months and 21 days post vaccination. Antibodies against equine influenza were measured by single radial haemolysis. Transient fever and injection site reactions were observed in several horses vaccinated with each vaccine. Only two horses failed to seroconvert post booster vaccination but there was a delayed response to the recombinant vaccine. The antibody response to the recombinant vaccine was lower than that induced by the whole-inactivated and subunit vaccines up to three months post vaccination. Thereafter, there was no significant difference. By six months post vaccination, the majority of horses in all three groups were clinically but not virologically protected. There was minimal decline in antibody titres within the 21-day grace period.

Durability of the neutralizing antibody response to vaccine and non-vaccine HPV types 7 years following immunization with either Cervarix® or Gardasil® vaccine

Bivalent (Cervarix®) and quadrivalent (Gardasil®) Human Papillomavirus (HPV) vaccines demonstrate remarkable efficacy against the targeted genotypes, HPV16 and HPV18, but also a degree of cross-protection against non-vaccine incorporated genotypes, HPV31 and HPV45. These outcomes seem to be supported by observations that the HPV vaccines induce high titer neutralizing antibodies against vaccine types and lower responses against non-vaccine types. Few data are available on the robustness of the immune response against non-vaccine types. We examined the durability of vaccine and non-vaccine antibody responses in a follow up of a head-to-head study of 12–15 year old girls initially randomized to receive three doses of Cervarix® or Gardasil® vaccine. Neutralizing antibodies against both vaccine and non-vaccine types remained detectable up to 7 years following initial vaccination and a mixed effects model was used to predict the decline in antibody titers over a 15 year period. The decline in vaccine and non-vaccine type neutralizing antibody titers over the study period was estimated to be 30% every 5–7 years, with Cervarix® antibody titers expected to remain 3–4 fold higher than Gardasil® antibody titers over the long term. The antibody decline rates in those with an initial response to non-vaccine types were similar to that of vaccine types and are predicted to remain detectable for many years. Empirical data on the breadth, magnitude, specificity and durability of the immune response elicited by the HPV vaccines contribute to improving the evidence base supporting this important public health intervention. Original trial: ClinicalTrials.gov NCT00956553.

Status of adult immunity to hepatitis A virus in healthcare workers from a tertiary care hospital in north India.

Background & objectives:Humans are considered to be the principal host for hepatitis A virus (HAV) infection. In India, heterogeneous groups of susceptible individuals coexist in different regions. There has been a decline in antibody titres to HAV among young adults which may pose a major public health problem. The objective of this study was to assess the IgG anti-HAV level among healthcare workers (HCWs) in the age group of 20-60 yr and its association with the socio-demographic variables.Methods:Blood sample (2 ml) was collected under aseptic conditions from each participant followed by the preparation of serum and storing at −20°C. ELISA-based kits were used for the determination of IgG antibodies to HAV in the human serum samples.Results:Two hundred and fifty four HCWs were enrolled. IgG anti-HAV antibodies were detected in 97.2 per cent of the samples analyzed. No differences were observed in the levels of IgG anti-HAV antibody and education, income, occupation and socio-economic classes of the HCWs. A seropositivity rate of over 90 per cent was seen amongst all the socio-economic classes.Interpretation & conclusions:High levels of IgG protective antibodies were seen among the studied HCWs, hence HAV vaccination may not be required. It will be advisable to do a cost-benefit analysis of vaccination for HAV.

IMMUNOGENICITY OF ADJUVANT INFLUENZA VACCINE FOR PREGNANT WOMEN

Recent epidemiological events showed that pregnant women are the most vulnerable part of population if there is the flu in the country and they die much more often than the rest part of people. That is why influenza vaccination of population including pregnant women is one of the priorities of public health service in our state. Worldwide experience of influenza vaccination of either adults or children by new adjuvant vaccine has caused our research of its efficiency among pregnant women. The aim of the study was to investigate the level of antibodies to influenza virus strain A/H1N1/v, A/H3N2 and B in pregnant women vaccinated adjuvant trivalent subunit vaccine. Our research is randomized and comparative on parallel groups. It was carried out within the demands of Russian Federation and International ethic norms adapted to such kind of researches. Evaluation of the immunogenicity of the vaccine was conducted in 27 pregnant women in the II trimester of gestation, and in 23 pregnant women in the III trimester of gestation, 19 non-pregnant women was in the control group. The level of antibodies in the serum was determined using a reaction of hemagglutination inhibition before and 1, 3, 6, 9 and 12 months after the vaccination. Revealed that influenza vaccination of pregnant women in the II and III trimester, causes the increase in titers of antibodies to vaccine influenza strains A and B, to fully meet the required criteria CPMP, and does not differ from the nonpregnant group. In a month after vaccination the level of seroprotective against A/H1N1/v was 77.0%, A/H3N2 — 88.9%, B — 85.2% after vaccination in II trimester, and 87.0; 87.0; 91.35% in III trimester of gestation. The factor of seroconversion after vaccination in II trimester for A/H1N1/v was equal to 6.5, A/H3N2 — 7.2, B — 6.5, after vaccination in III trimester of pregnancy: 7.1, 6.5 and 5.1 correspondingly. At the same time revealed accelerated decline in antibody titer against influenza in pregnant women compared to nonpregnant women in a year after immunization The set of results of the study can be concluded that adjuvant trivalent subunit vaccine effective in vaccination of pregnant women in II and III trimester of pregnancy, and it is able to effectively provide immune protection against viruses of the flu A and B within all pregnancy long.

Decrease in Anti-HBs Antibodies over Time in Medical Students and Healthcare Workers after Hepatitis B Vaccination.

Background Hepatitis B is one of the most important occupational hazards among healthcare workers (HCWs). This study aimed to measure the anti-HBs titres among the medical students and HCWs vaccinated against hepatitis B virus and to determine the association between anti-HBs levels and time since vaccination. Materials and Methods In this cross-sectional study, medical students and healthcare workers who had received all three doses of hepatitis B vaccination and completed at least six months after vaccination since the last dose were included. 3 ml blood was collected from subjects (n = 340) and anti-HBs titre was estimated using ELISA. Results A total of 340/400 subjects were aged between 18 and 60 years; 204 were females and 136 males. The median and interquartile range for time since vaccination were 5 and 5 years, respectively. Duration since vaccination was ≤5 years in 223 (65.5%), 6–10 years in 84 (24.7%), and >10 years in 33 (9.70%); among them, antibody titres were >10 mIU/ml in 94.1%, 79.7%, and 72.7% subjects, respectively. There was significant decline in antibody titres as duration of postvaccination increased. Conclusion The proportion of subjects who were unprotected after 5 and 10 years after vaccination were 20% and 27%, respectively. The need for a booster dose can be made mandatory at least for healthcare professionals.

Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans

Despite the availability of safe and effective human vaccines, rabies remains a global threat, with an estimated 60,000 human deaths annually attributed to rabies. Pre-exposure prophylaxis against rabies infection is recommended for travelers to countries where rabies is endemic, and also for those with a higher risk of exposure. In this study, the rabies-specific neutralising antibody responses in a cohort of rabies-vaccinated recipients over a period of twenty years have been assessed. In particular, the antibody response to primary vaccinations and boosters, and the waning of antibody post primary vaccination and post booster were investigated. The significance of gender, age at vaccination, vaccine manufacturer and vaccination intervals were also evaluated. These data confirm that rabies vaccination can elicit a neutralising antibody response that can remain at detectable levels for a number of years, without additional booster vaccinations. The antibody response following both primary vaccination and booster was significantly influenced by the gender of the subject (p=0.002 and 0.03 respectively), with supportive data that suggests an effect by the make of vaccine administered following primary vaccination, with significantly higher VNA titres observed for one vaccine manufactured prior to 2006 (p<0.001) in a small subset of recipients (n=5). Additionally, the decay rate was demonstrated through the overall decline in antibody titre for all individuals, which was a 37% and 27% reduction per 2-fold change in time following primary and booster vaccination respectively. Individuals within older age groups demonstrated a significantly faster decline in antibody titre following the primary vaccination course (p=0.012). Rate of decline in antibody titre was also significantly influenced by the vaccine make following primary course (p<0.001). The assessment of neutralising antibody titre decline has also provided an insight into the most appropriate timing for booster administration, and enabled the prediction of long term titres from post-vaccination antibody titres.

Immune responses to a recombinant, four-component, meningococcal serogroup B vaccine (4CMenB) in adolescents: A phase III, randomized, multicentre, lot-to-lot consistency study

BackgroundFor decades, a broadly effective vaccine against serogroup B Neisseria meningitidis (MenB) has remained elusive. Recently, a four-component recombinant vaccine (4CMenB) has been developed and is now approved in Europe, Canada, Australia and some Latin American countries. This phase III, randomized study evaluated the lot consistency, early immune responses and the safety profile of 4CMenB in 11 to 17-year-old adolescents in Australia and Canada (NCT01423084). MethodsIn total, 344 adolescents received two doses of one of 2 lots of 4CMenB, 1-month apart. Immunogenicity was assessed before, 2-weeks and 1-month following the second vaccination. Serum bactericidal activity using human complement (hSBA) was measured against three reference strains 44/76-SL, 5/99 and NZ98/254, selected to express one of the vaccine antigens; Neisseria adhesin A (NadA), factor H binding protein (fHbp) and porin A (PorA) containing outer membrane vesicle (OMV), respectively. Responses to the Neisseria heparin binding antigen (NHBA) were assessed with enzyme linked immunosorbent assay (ELISA). Local and systemic reactions were recorded for 7 days following each vaccination; unsolicited adverse events were monitored throughout the study. ResultsImmunological equivalence of the two lots of 4CMenB was established at 1-month. At baseline, ≤7% of participants had hSBA titers ≥5 to all three reference strains. Two weeks following the second dose of 4CMenB, all participants had hSBA titers ≥5 against fHbp and NadA compared with 84–96% against the PorA reference strains. At 1-month, corresponding proportions were 99%, 100% and 70–79%, respectively. Both lots were generally well tolerated and had similar adverse event profiles. ConclusionsTwo doses of 4CMenB had an acceptable safety profile and induced a robust immune response in adolescents. Peak antibody responses were observed at 14 days following vaccination. While a substantial non-uniform antigen-dependent early decline in antibody titers was seen thereafter, a significant percentage of participants continued to maintain protective hSBA titers at 1-month.

Antibody persistence after primary and booster doses of a quadrivalent meningococcal conjugate vaccine in adolescents.

The aim of this study was to evaluate antibody persistence 5 years after primary vaccination with the quadrivalent meningococcal conjugate vaccines MenACWY-CRM or MenACWY-D and 2 years after a booster dose of MenACWY-CRM, in the context of a phase 3 study. Subjects (aged 19.2 ± 2.3 years) were assigned to 5 groups according to whether they had previously received primary vaccination (at 14.2 ± 2.2 years) with MenACWY-CRM (N = 131) or MenACWY-D (N = 76), a booster dose of MenACWY-CRM 3 years after primary vaccination with MenACWY-CRM (N = 44) or MenACWY-D (N = 31) or no vaccination (N = 107). The immunogenicity measures were percentages of subjects with serum bactericidal activity (hSBA) ≥ 1:8 for serogroups A, C, W and Y and hSBA geometric mean titers. Comparisons with age-matched, vaccine-naive subjects were performed. A majority of subjects vaccinated 5 years previously maintained hSBA ≥ 1:8 against serogroups C, W and Y in the MenACWY-CRM (59%-82%) and MenACWY-D groups (54%-73%); this was lower for serogroup A in both groups. There was a decline in antibody titers after primary vaccination, especially in the first 2 years postprimary vaccination, with steady concentrations during the next 3 years. Two years after MenACWY-CRM booster vaccination the percentages of subjects with hSBA ≥ 1:8 ranged from 77% to 100% across serogroups and geometric mean titers were 2.5- to 8-fold higher than prebooster values across serogroups. Booster vaccination with MenACWY-CRM elicited a robust immune response during the 2-year follow-up period, irrespective of previous vaccination.