Antibody Seroconversion Rates Research Articles

Antibody Responses to SARS-CoV-2 Infection in Cancer Patients

Background: Literature is sparse about the prevalence and durability of immune response to infection with Severe Acute Respiratory Syndrome Coronavirus 2( SARS-CoV-2 ) / Coronavirus Disease (COVID-19) in cancer patients. Method: We retrospectively analyzed antibody levels and seroconversion rates in serum samples from 135 cancer patients recovered from SARS-CoV-2 infection. Chemiluminescent Immunoassay (CLIA) using Roche Cobas e801 analyzer (Roche Diagnostics, Rotkreuz, Switzerland) was performed to identify Pan Ig antibody against Nucleocapsid Antigen. Reports of 1st, 3rd and 6th month were analyzed. Seroconversion was also compared with health care workers (HCW) of our institute who had recovered from COVID-19 infection. Findings: Seroconversion rate in cancer patients was 81.2% at 1 month, 95% at 3 months and 94.6% at 6 months post RT-PCR positivity. There was no difference in seroconversion rate among different age groups, gender, co-morbidities, severity of COVID-19 symptoms, cancer disease status and treatment with chemotherapy. Seroconversion rate in cancer patients is comparable to HCW (90.4% vs 96%, p=0.82) and is durable. Interpretation: Humoral response to COVID-19 infection in cancer patients is comparable to general population and sustained. Such responses suggest that cancer patients are likely to benefit from COVID-19 vaccination. Funding: Not applicableDeclaration of Interests: No financial and personal conflict of interest.Ethics Approval Statement: The study protocol was reviewed and approved by institute ethics committee.

Safety and Immunogenicity of a SARS-CoV-2 Inactivated Vaccine Administered Simultaneously with an Inactivated Quadrivalent Influenza Vaccine: A Randomized, Open-Label, Controlled Study in Healthy Adults Aged 18 to 59 Years in China

Background: Studies are needed to provide evidence for the immunization strategy of the COVID-19 vaccine simultaneously administered with the influenza vaccine. Methods: A randomised, open-label, controlled, phase 4 clinical trial was conducted in Zhejiang Province, east of China. Eligible healthy adults aged 18–59 years underwent randomization at a ratio of 1:1:2 to receive one dose of inactivated quadrivalent influenza vaccine (IIV4) either simultaneously with the first (SI1 subgroup, Day 0) or the second (SI2 subgroup, Day 28) dose of CoronaVac, or 14 days after the first dose of CoronaVac (SE group). The primary endpoint of the study was the non-inferiority in seroconversion rate of antibody against SARS-Cov-2 between participants who received two vaccines simultaneously and those who followed the separate vaccination schedule (clinicaltrials.gov number, NCT04801888). Findings: Overall, 480 participants were enrolled, with 120, 120, and 240 randomly assigned to the SI1, SI2, and SE groups, respectively. With the noninferiority margin set at 10%, the seroconversion of antibodies against SARS-CoV-2 in the SI group (93.11% [89.04, 96.01]) was not inferior to that in the SE group (95.15% [91.50, 97.56]) in the per-protocol set. Overall, the geometric mean titer (GMT) in the SE group was higher than that in the SI group with statistical significance (38.06 vs. 27.54, P=0.0001). Within the SI group, the GMT was significantly higher in the SI1 subgroup than that in the SI2 subgroup (32.61 vs 23.26, P=0.0153). The occurrences of vaccine related adverse reactions were comparable among different vaccination groups (16.67% vs. 19.17% and 20.00%, P=0.7568).Interpretation: Simultaneous administration of both SARS-Cov-2 inactivated vaccine and seasonal influenza vaccine would be feasible. Further studies are needed to explain the unexpected decrease of immune response against SARS-CoV-2 following the regimen that IIV4 simultaneously administered with the 2 nd dose of the SARS-CoV-2 inactivated vaccine.Trial Registration: This study was registered at: (clinicaltrials.gov number, NCT04801888).Funding: This study was funded by the Vaccine Clinical Evaluation Platform Construction Project under China National Science and Technology Major Projects [2018ZX09734004] and The Key Research and Development Program of Zhejiang Province (2021C03200).Declaration of Interest: GZ, XD and ZW are employees of Sinovac Biotech CO., Ltd. All other authors declare no competing interests.Ethical Approval: The study protocol and informed consent form were approved by the ethics committee of the Zhejiang Provincial Center for Disease Control and Prevention (ZJCDC).

Seroprevalence of COVID-19 infection among healthcare professionals in Central India using SARS-CoV-2 antibody test

The diagnosis and monitoring of SARS-CoV-2 infection (COVID-19 illness) are based on two different types of tests: (i) RT-PCR (reverse-transcription polymerase chain reaction) test that detects the presence of viral RNA, and (ii) antibody test that detects antibodies to SAR-CoV-2. Studies have demonstrated that antibody testing is useful for the identification of asymptomatic or subclinical infection of SARS-CoV-2 among close contacts with COVID-19 patients, including the HCP.This study presents the first SARS-CoV-2 seroprevalence study among 307 HCP in Central India. This study also evaluates the risk of exposure of the HCP of different roles/departments to COVID-19 infection by the SARS-CoV-2 antibody seroconversion rate. A cross-sectional study was conducted using serum obtained from 307 HCP, who were on duty in the hospitals in Indore City of Central India during the COVID-19 pandemic from March till June 2020. Siemens Healthineers COV2T assay that detects total antibody (including IgM and IgG) against the S1-RBD (receptor binding domain of spike protein subunit 1) antigen was selected to be used in this study due to its robust sensitivity and specificity, compared to IgG or IgM assay alone Overall, the prevalence of COVID-19 infection among HCP in Central India hospital is 7.82% (n=24/307) as evaluated using SARS-CoV-2 total antibody test. Of the 307 HCP. Seropositivity rate varies widely by professions/departments ranging from intensivists (66.7%), general surgeons (25%), ophthalmologist (20%), pediatrician (20%), anesthetist (12.5%), radiologist (10%), general physician (9.7%) to gynaecologist (4.9%). This seroprevalence study, along with other studies, highlights the importance of SARS-CoV-2 antibody in seroprevalence and epidemiology studies which may subsequently guide the policy-making in implementing an effective infection control strategy to curb SARS-CoV-2 transmission in the hospital settings; on top of the use as aid-in-diagnosis, contact-tracing, pre and post vaccination screening and evaluation of convalescent plasma therapy.

Neutralizing antibody against Enterovirus-A71 in Thai children: A longitudinal study from birth to age 4 years

Thailand is one of the countries in the Asia-pacific region that has been most affected by the Enterovirus-A71 (EV-A71) epidemic. An individual who is susceptible to EV-A71 may also be infected asymptomatically, thus, a serological assay is a useful tool to estimate the cumulative incidence of infection in the community and to provide guidance for vaccination scheduling. There have been several candidate EV-A71 vaccines, of which three have been approved and licensed in China. The population target for EV-A71 vaccine is children younger than three years of age. In Thailand, there are limited data available on the seroprevalence of EV-A71 neutralizing (NT) antibodies and the timing of seroconversion in children. This study aims to investigate the seroprevalence and seroconversion rate of EV-A71 NT antibody in a cohort of Thai children. Sera were collected at the King Chulalongkorn Memorial Hospital in Bangkok, Thailand from 100 children between 2015 and 2020. Maternal sera were collected on the day of delivery. Serum samples from children were collected at birth (month 0) and at 2, 7, 18, 24, 36, and 48 months of age to test for EV-A71 NT antibody titers using an enzyme-linked immunosorbent assay (ELISA)-based microneutralization test. The seroprotection rate (NT antibody ≥1:16) in children at months 0, 2, 7, 18, 24, 36, and 48 was 81.0%, 60.0%, 9.0%, 10.0%, 13.0%, 17.0%, and 37.1%, respectively. The seroprotection rate was lowest at month 7 due to waning of the maternal antibody and the immunity of children increased with increasing age. At 48 months of age, less than 40% of children were seroprotected. Children at the age of 6 months should be considered a primary target for vaccination.

Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients.

Hematopoietic stem cell transplantation (HSCT) recipients require hepatitis B (HBV) revaccination. Hepatitis B surface antibody (anti-HBs) seroconversion rates after revaccination range from 64% to 79% in these patients. The seroconversion rate and factors associated with non-seroconversion have not been clearly elucidated in pediatric and young adult recipients after HSCT. To evaluate anti-HBs seroconversion rates in pediatric and young adult patients revaccinated after HSCT, and to identify factors associated with non-seroconversion. The current study was prospective and cross-sectional. Post-HSCT recipients aged ≤25years who had completed a course of three HBV revaccinations were recruited, and their anti-HBs titers were assessed. Non-seroconverted patients were administered a fourth vaccination. Those who subsequently remained seronegative were administered two additional vaccinations. Those who remained seronegative after all six vaccinations were defined as non-responders. A total of 118 patients were enrolled. The HBV-containing vaccines used included DTaP-IPV-HBV-Hib, DTwP-HBV-Hib, and monovalent vaccines. The anti-HBs seroconversion rate after three revaccinations was 82% (95% confidence interval [CI], 73.7-89.2). One patient (0.8%) was classified as non-responder. Factors associated with non-seroconversion after three revaccinations included cytomegalovirus (CMV) reactivation (odds ratio [OR] 10.63, 95% CI 1.16-97.00), anti-HBs seronegativity before HSCT (OR 7.01, 95% CI 1.55-31.78) and three DTwP-HBV-Hib revaccinations (OR 11.71, 95% CI 1.43-96.26). In the current study the anti-HBs seroconversion rate after three HBV revaccinations was excellent. CMV reactivation, anti-HBs seronegativity before HSCT, and three DTwP-HBV-Hib revaccinations were associated with non-seroconversion, but the non-responder rate was low.

The effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines

BackgroundMaternal poliovirus antibodies could provide passive immunity to the newborns from poliovirus infection during their first few months of life, but they may impair the immune responses of infants to the poliovirus vaccine as well. In our study, we pooled the data from three clinical trials of the inactivated poliovirus vaccine (IPV) based on Sabin strains to investigate the effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines.MethodsThere were five groups in the pooled analysis, including low-dose Sabin IPV, medium-dose Sabin IPV, high-dose Sabin IPV, control Sabin IPV, and control Salk IPV groups. We reclassified the infants in different groups according to their maternal poliovirus antibodies by two methods, the first one included maternal antibody negative (< 1:8) and maternal antibody positive (≥1:8), and the second one included maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32. Then, we compared the geometric mean titers (GMTs), geometric mean antibody fold increases (GMIs) and seroconversion rates of poliovirus type-specific neutralizing antibodies after vaccination among participants with different maternal poliovirus antibody levels.ResultsThe GMTs and GMIs of three types of poliovirus antibodies after vaccination in maternal antibody negative participants were significantly higher than those in maternal antibody positive participants. The seroconversion rates of type II and type III poliovirus antibodies in maternal antibody positive participants were significantly lower than those in maternal antibody negative participants. Among participants with maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32, the GMTs and GMIs of three types of poliovirus antibodies after vaccination showed a tendency to decline with the increasing of maternal antibody levels. The seroconversion rates of three types of poliovirus antibodies in participants with maternal antibody titer ≥1:32 were significantly lower than those in participants with maternal antibody titer < 1:8 and 1:8 ~ < 1:32.ConclusionsMaternal poliovirus antibodies interfered with the immune responses of infants to poliovirus vaccines, and a high level of maternal antibodies exhibited a greater dampening effect.Trial registrationClinicalTrials.govNCT04264598 February 11, 2020; ClinicalTrials.govNCT04264546 February 11, 2020; ClinicalTrials.govNCT03902054 April 3, 2019. Retrospectively registered.

Immunogenicity and safety of purified vero cell-cultured rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in the healthy Chinese subjects: a randomized, double-blind, positive controlled phase 3 clinical trial

ABSTRACT Aim: The aims of the study were to evaluate the non-inferiority of the safety and immunogenicity of a new trial purified vero cell-cultured rabies vaccine (trial vaccine) in healthy subjects comparing with the control purified vero cell-cultured rabies vaccine (control vaccine) following Essen regimen and to evaluate the non-inferiority of the safety and immunogenicity of the trial vaccine following two intramuscular regimens, between Zagreb and Essen regimen. Methods: Serum samples were collected before vaccination and on d 7, 14, 35/42 post vaccination. Adverse events (AEs) were recorded for 30 d following each vaccination. This study was registered in the Chinese Clinical Trial Registry (ChiCTR-PPR-15007057). Results: There was no significant difference in the incidence of AEs, local and systemic reactions, among Zagreb group, Essen group, and control group. But the incidence of solicited AEs was a significant difference among the three groups (p = 0.0498). The incidence of solicited AEs was higher in Essen group than that in control group and Zagreb group (p = 0.0278, p = 0.0248). In the subjects whose antibodies were seronegative before vaccination, the seroconversion rates of antibodies among three groups were all 100.0% on d 14 and d 35/42. The Essen group was not inferior to the control group, and the Zagreb group was not inferior to the Essen group on d 14. On d 14 and d 35/42, the geometric mean concentration of the three groups was much higher than the immune protection level of 0.5 IU/ml. Conclusions: The trial vaccine had good safety and immunogenicity, and the trial vaccine is not inferior to the control vaccine. Abbreviations: PVRV: purified vero cell-cultured rabies vaccine; AE: adverse event; CI: confidence interval; GMC: geometric mean concentration; IM: intramuscular; NIFDC: National Institutes for Food and Drug Control; PPS: per-protocol set; SS: safety set; REFIT: Rapid Fluorescent Focus Inhibition Test; RVNA: rabies virus neutralizing antibody; WHO: World Health Organization.

Maternal Secretor Status Affects Oral Rotavirus Vaccine Response in Breastfed Infants in Bangladesh.

Secretor status controls mucosal histo–blood group antigen expression and is associated with susceptibility to rotavirus (RV) diarrhea, with nonsecretors less susceptible to symptomatic infection. The role of breast milk secretor status on oral live-attenuated RV vaccine response in breastfed infants has not been explored. In a monovalent G1P[8] RV vaccine (Rotarix) trial in Bangladesh, RV-specific plasma immunoglobulin A antibody seroconversion rates were higher among infants of maternal nonsecretors (39%) than infants of maternal secretors (23%; P = .001). Maternal status remained a significant predictor when correcting for infant status (P = .002). Maternal secretor status should be considered when interpreting oral RV vaccine responses in low- and middle-income settings.Clinical Trials Registration. NCT01375647.

Safety and efficacy of human papillomavirus vaccination for people living with HIV: A systematic review and meta-analysis.

The current evidence regarding the safety and immunogenicity of human papillomavirus (HPV) vaccinations for people living with HIV (PLWH) is unclear. We searched PubMed, Embase, Cochrane Library and Web of Science databases from inception to 23 November 2018. The pooled proportion, relative risk (RR) and the standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated. Twenty-four studies consisting of 7507 participants were identified. The pooled proportion of adverse events in HIV-infected vaccinees was 60% and the antibody seroconversion rates in HPV-6, -11, -16, -18 subtypes were all above 90%. When compared with the placebo groups, the risk of adverse events was not different except for the injection site reactions (RR: 2.63, 95% CI: 1.72–4.01, p &lt; 0.001), and the level of CD4 was relatively lower (SMD: −0.17, 95% CI: −0.29 to −0.04, p = 0.01) in the HIV-positive vaccinees groups. When compared with HIV-negative vaccinees, the risk of adverse events was not different, but the pooled RR and SMD indicated that antibody seroconversion and geometric mean titer for HPV-18 in HIV-positive groups was lower (RR: 0.91, 95% CI: 0.87–0.95, p &lt; 0.001; SMD: −0.43, 95% CI: −0.62 to −0.24, p &lt; 0.001). The study proves that HPV vaccine is safe and efficacious for PLWH and has important implications for international guidelines and strategies for HPV vaccination.

Immunogenicity and safety of an inactivated enterovirus A71 vaccine in children 3–6 years and 2–35 months of age- an open-label, randomized phase IIb clinical trial

BackgroundEnterovirus A71 (EV-A71) infection can cause severe debilitating complications and even death in young children. The immunogenicity and safety of an inactivated whole EV-A71 virus vaccine were assessed in children 2 months to 6 years of age. MethodsThis was an open-label, multi-center and randomized phase IIb study, which divided into part A and B. In part A, children 36 months to 6 years of age were enrolled and randomized into 3 groups, receiving 0.5 μg total viral protein (TP) with adjuvant Al(OH)3, 1.0 μg TP with Al(OH)3 or 1.0 μg TP only. Two doses of vaccines were administered at a 28-day interval and blood was taken before immunization, at week 4, 8, 28 and 52 (optional) for virus neutralization assay. Safety profiles were also monitored. After safety profiles had shown no concerns, children 2 months to 35 months of age (part B) were subsequently enrolled following the same protocol. ResultsA total of 135 children completed two doses of immunization, including 58 in part A and 77 in part B. Both adjuvanted 0.5 μg and 1.0 μg TP elicited significant raise of neutralizing antibody titers and seroconversion rate was up to 93.75–100.0% after 2 doses of immunization. Adjuvanted 1.0 μg TP induced higher titers of neutralizing antibodies than adjuvanted 0.5 μg TP. By contrast, non-adjuvanted 1.0 μg TP was not immunogenic. No major adverse events were reported. ConclusionsThis EV-A71 vaccine containing adjuvant is immunogenic and safe in children 2 months to 6 years of age.Clinical Trials Registration.NCT03268083.

Preliminary evaluation of adjuvant effects of cyclic dinucleotides (CDN) on immune responses to nasal spray influenza vaccine

Objective To analyze the immunostimulatory effects of cyclic dinucleotides (CDN) on immune responses to a nasal spray influenza split virus vaccine and to evaluate its potential as a mucosal adjuvant. Methods A H1N1 influenza split virus vaccine combined with different CDN was used for mouse immunization. Each mouse was intranasally immunized twice with 4.5 μg of hemagglutinin (HA) and 10 μg of CDN with an interval of 21 d. Titers of hemagglutination inhibition (HI) antibodies in serum, secretory IgA (sIgA) in bronchoalveolar lavage fluid and IgG in serum were detected 21 d after the last immunization. Immunostimulatory activities of different CDN were compared. Effects of cyclic di-GMP (c-di-GMP) and chitosan (CSN) on the immunogenicity of H1N1 and H7N9 influenza split vaccines were analyzed and compared. H1N1 influenza split vaccine combined with c-di-GMP or CSN was used to immunize mice. Three weeks after the last immunization, these mice were challenged with 10 times the median lethal dose (LD50) of A/Puerto Rico/8/34 (H1N1) influenza virus. Survival rates of the mice were observed for 14 d. Results All three CDN induced high levels of HI antibodies and IgG in serum and sIgA in BALF. HI antibody seroconversion rates were also higher than those of the control groups. c-di-GMP was superior to CSN in enhancing the immunogenicity of H1N1 and H7N9 antigens as higher titers of HI antibodies in serum and sIgA in BALF were induced. Conclusions CDN could enhance the immunogenicity of influenza antigens with better efficacy than CSN adjuvant. Key words: Cyclic dinucleotide; Adjuvant; Chitosan; Immunogenicity

Measurement of anti-influenza neuraminidase antibody induced by H7N9 influenza vaccine

Objective To develop an enzyme-linked lectin assay (ELLA) for measuring neuraminidase inhibition (NI) antibody titers in subjects vaccinated with H7N9 influenza vaccine. Methods Neuraminidase substrate, the dilution and incubation time of enzyme-labeled antibody, the concentration of influenza antigen for coating and pH value of the dilution buffer were optimized. Based on that, ELLA was established and used to detect anti-influenza neuraminidase antibody titers in serum samples of 34 subjects before and after vaccination with H7N9 influenza vaccine. Results The optimal neuraminidase substrate was fetuin at a coating concentration of 7.5 μg/ml. The optimal dilution of enzyme-labeled antibody was 1∶500. The virus strain of influenza H7N9 vaccine was used as antigen at a concentrations of 4.5lgCCID50/ml in solution with a pH of 6.5. Influenza-specific NI titers detected after immunization with vaccine were significantly higher than those before vaccination (P<0.001). In the 34 subjects receiving H7N9 vaccine, the seroconversion rate of NI antibody was 47% (≥40 in NI titer ), which was lower than that of HI antibody (P<0.05). Conclusions An ELLA with natural substrate for measurement of anti-influenza NI antibody was developed. It is simple and practical and might be used in the establishment of immune evaluation system for influenza vaccines and NI antibody. Key words: H7N9 influenza vaccine; Neuraminidase inhibition antibody; ELLA

One year immunogenicity and safety of subunit plague vaccine in Chinese healthy adults: An extended open-label study

ABSTRACTBackground: To evaluate the one-year immunogenicity and safety of a subunit plague vaccine. Methods: In the initial study, 240 healthy adults aged 18–55 years were administrated with 2 doses of 15 or 30 µg plague vaccines at day 0 and 28, respectively. In this extended follow-up study, we evaluated the immunogenicity and safety of the plague vaccine up to one year. Results: For antibody to envelope antigen faction 1 (F1) antigen, titers were up to new peaks at month 6, then declined slowly to month 12, but remained at higher levels than those at day 56. Geometric mean titers (GMTs) of F1 were significantly higher in 30 µg group than those in 15 µg group at month 6 and 12 (P < 0.0001 and P < 0.001). However, approximate 100% seroconversion rates of F1 antibodies were found in both 15 and 30 µg groups at the both time points. For antibody to recombinant virulence (rV) antigen, titers and seroconversion rates were decreased sharply at month 6 and continue to decrease at month 12. GMTs and seroconversion rates were not significantly different between the 15 and 30 µg groups, respectively. No serious adverse events (SAEs) related to vaccine occurred. Conclusion: The new plague vaccine (F1+rV) induced a robust immune response up to 12 months and showed a good safety profile in adults aged 18–55 years.

Immunogenicity and Safety of Co-Administered Live Attenuated Japanese Encephalitis SA 14-14-2 Vaccine and Measles-Rubella Vaccine Compared with Measles-Rubella Vaccine Alone in Infants 8 Months of Age, China

Background: Measles is one of the most contagious diseases ever known and is an important cause of death and disability among young children worldwide. Rubella is generally a mild disease in children and adults, but rubella virus infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or infants with a constellation of congenital malformations known as congenital rubella syndrome. A growing number of countries are adopting the use of the combined measles-rubella vaccine (MR) to prevent both diseases. In China, measles-rubella vaccine and live, attenuated SA-14-14-2 Japanese encephalitis vaccine (LJEV) are recommended for simultaneous administration at age 8 months, which is the earliest recommended age globally. Evidence is limited whether co-administering MR and LJEV at 8 months of age will impact immunogenicity of MR antigens. Methods: We conducted a prospective, two-arm randomized trial between August 2015 and June 2016 in two provinces in China to determine whether at 8 months of age, seroconversion to measles antibody and rubella antibody 6 weeks after co-administration of MR and LJEV was non-inferior to seroconversion 6 weeks after administration of MR without LJEV. Measles immunoglobulin G (IgG) and rubella IgG antibody levels were determined using an enzyme-linked immunosorbent assay on blood samples collected before vaccination and six weeks (42-48 days) post-vaccination. For non-inferiority tests, we calculated a two-sided, 90% (Farrington-Manning) confidence bound of the difference in antibody levels between persons who received MR LJEV and those who received MR alone. Solicited and unsolicited adverse events following immunization (AEFI) were recorded for all infants who completed the study. Findings: Of 1,093 enrolled infants, 507 in the MR LJEV group and 506 in the MR-only group completed the study. Before vaccination, 1.2% in MR LJEV group and 0.2% in the MR-only group were seropositive for measles antibody (p=0.13); 1.6% in MR LJEV group and 0.4% in the MR-only group were seropositive for rubella antibody (p=0.11). Six weeks after vaccination, measles antibody seroconversion rates were 97.8% in the MR LJEV group compared to 98.6% in the MR-only group (non-inferior; p<0.0001). Six weeks after vaccination, rubella antibody seroconversion rates were 94.3% in the MR LJEV group compared to 93.5% in the MR-only group (non-inferior; p<0.0001). Mild local reactions included redness, swelling and pain; systemic reactions included fever, diarrhea and vomiting. There were no serious non-fatal or fatal AEFIs. Interpretation: The high seroconversion rates, non-inferiority, and safety of co-administered LJEV and MR found in this randomized trial provide support for the co-administration of these live attenuated vaccines in infants, a finding of importance to the global priorities of measles elimination and expansion of JE vaccination in endemic countries. Funding: Centers for Disease Control and Prevention, US Department of Health and Human Services. 2014-2015 Research Program Seven, China-US Collaborative Program on Emerging and Reemerging Infectious Diseases. Conflict of Interests: The authors declare that they have no competing interests. Ethical Approval Statement: This study was approved by the Ethical Review Committee of Chinese Center for Disease Control and Prevention (approval number: 201518); US CDC was designated as a non-engaged collaborator for Institutional Review Board purposes. Parents or legal guardians of participating infants signed an informed consent prior to study enrollment and allocation to study group.

Immunological Effect of aGV Rabies Vaccine Administered Using the Essen and Zagreb Regimens: A Double-Blind, Randomized Clinical Trial.

This study evaluated the immunological effect of an aGV rabies virus strain using the Essen and Zagreb immunization programs. A total of 1,944 subjects were enrolled and divided into three groups: the Essen test group, Essen control group, and Zagreb test group. Neutralizing antibody levels and antibody seroconversion rates were determined at 7 and 14 days after the initial inoculations and then 14 days after the final inoculation in all of the subjects. The seroconversion rates for the Essen test group, Essen control group, and Zagreb test group, which were assessed 7 days after the first dosing in a susceptible population, were 35.74%, 26.92%, and 45.49%, respectively, and at 14 days, the seroconversion rates in this population were 100%, 100%, and 99.63%, respectively. At 14 days after the final dosing, the seroconversion rates were 100% in all three of the groups. The neutralizing serum antibody levels of the Essen test group, Essen control group, and Zagreb test group at 7 days after the first dosing in the susceptible population were 0.37, 0.26, and 0.56 IU/mL, respectively, and at 14 days after the initial dosing, these levels were 16.71, 13.85, and 16.80 IU/mL. At 14 days after the final dosing, the neutralizing antibody levels were 22.9, 16.3, and 18.62 IU/mL, respectively. The results of this study suggested that the aGV rabies vaccine using the Essen program resulted in a good serum immune response, and the seroconversion rates and the neutralizing antibody levels generated with the Zagreb regimen were higher than those with the Essen regimen when measured 7 days after the first dose.

Humoral Immune Response to Peste des Petits Ruminants Vaccination in West African Dwarf Sheep Experimentally Infected with Trypanosoma congolense and Treated with Trypanocide

This study was conducted to assess the humoral immune response to Peste des petits ruminants (PPR) vaccination in West African Dwarf (WAD) sheep experimentally infected with Trypanosoma congolense (Tc). Twenty adult WAD sheep, assigned to five (5) groups of four (4) sheep each were used. Group A sheep were neither vaccinated nor infected, while all sheep in groups B-E were vaccinated using PPR vaccine. Sheep in groups D and E were then infected with 5 x 105 trypanosomes per ml of Tc one (1) week post vaccination (PV) while sheep in groups C and D were treated at 3 weeks post infection with diminazene aceturate. A prepatent period of 12-14 days was observed and antibody titres detectable at one (1) week PV in all vaccinated sheep. The antibody levels progressively increased to a peak Geometric mean titre (GMT) values of 181.0, 222.9, 78.8 and 4.0 for groups B, C, D and E respectively at 8 week PV. Parasitaemia was followed by a depressed sero-conversion rate of antibody. Treatment however enabled the vaccinated Tc infected sheep to mount antibody responses that was superior to that of the infected untreated group. The effectiveness of PPR control programme in trypanosomosis endemic areas could be undermined by trypanosome-induced immunosuppression. Even so, this could be ameliorated by effective trypanocide chemotherapy.

Immune response to hepatitis B vaccine in patients with chronic hepatitis C infection: A systematic review and meta-analysis.

Hepatitis B virus and hepatitis C virus (HCV) co-infection can add to the severity of hepatitis and the risks of liver cirrhosis and hepatocellular carcinoma. Whether chronic HCV infection decreases antibody response to hepatitis B vaccination is still controversial. We evaluate the influence of HCV infection on antibody response to hepatitis B vaccination by a systematic review of published works with a meta-analysis of clinical trials. The random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses were used in this study. The end-point of interest was the rate of patients showing seroconversion of antibody responses at completion of hepatitis B vaccination schedule among patients with chronic HCV infection versus healthy controls. We identified 11 studies involving 704 patients with HCV and 812 controls. Our results show a significant decrease in antibody seroconversion rates among patients with HCV versus healthy controls (pooled odds ratio = 0.17 [95% confidence interval, 0.11-0.28]). The P-value was 0.21 for our test of study heterogeneity. Stratified analysis in subgroups of interest and sensitivity analysis did not meaningfully change our results. Our meta-analysis showed patients with hepatitis C infection have a statistically significant lower rate of seroconversion in comparison to healthy controls, both in cirrhotic and non-cirrhotic patients. Chronic HCV infection can decrease the immune response to a standard schedule of hepatitis B vaccination. Further studies are needed to investigate the optimum vaccination schedule for patients with chronic HCV infection.

Effects of prior influenza virus vaccination on maternal antibody responses: Implications for achieving protection in the newborns

In the US, influenza vaccination is recommended annually to everyone ≥6months. Prior receipt of influenza vaccine can dampen antibody responses to subsequent vaccination. This may have implications for pregnant women and their newborns, groups at high risk for complications from influenza infection. This study examined effects of prior vaccination on maternal and cord blood antibody levels in a cohort of pregnant women in the US. Influenza antibody titers were measured in 141 pregnant women via the hemagglutination inhibition (HAI) assay prior to receipt of quadrivalent influenza vaccine, 30days post-vaccination, and at delivery (maternal and cord blood). Logistic regression analyses adjusting for age, BMI, parity, gestational age at vaccination, and year of vaccination compared HAI titers, seroprotection, and seroconversion in women with versus without vaccination in the prior year. Compared to those without vaccination in the previous year (n=50), women with prior vaccination (n=91) exhibited higher baseline antibody titers and/or seroprotection rates against all four strains after controlling for covariates. Prior vaccination also predicted lower antibody responses and seroconversion rates at one month post-vaccination. However, at delivery, there were no significant differences in antibody titers or seroprotection rates in women or newborns, and no meaningful differences in the efficiency of antibody transfer, as indicated by the ratio of cord blood to maternal antibody titers at the time of delivery. In this cohort of pregnant women, receipt of influenza vaccine the previous year predicted higher baseline antibody titers and decreased antibody responses at one month post-vaccination against all influenza strains. However, prior maternal vaccination did not significantly affect either maternal antibody levels at delivery or antibody levels transferred to the neonate. This study is registered with the NIH as a clinical trial (NCT02148874).

Immunologic response to vaccine challenge in pregnant PTPN22 R620W carriers and non-carriers.

ObjectivesInfluenza infection is a significant cause of respiratory morbidity among pregnant women. Seasonal influenza vaccination engages innate immune receptors to promote protective immunity. A coding polymorphism (R620W) in PTPN22 imparts elevated risk for human infection and autoimmune disease, predisposes to diminished innate immune responses, and associates with reduced immunization responses. We sought to quantify the effects of PTPN22-R620W on humoral and cell-mediated immune responses to the inactivated influenza vaccine among healthy pregnant women.Study DesignImmune responses were measured in healthy pregnant R620W carrier (n = 17) and non-carrier (n = 33) women receiving the 2013 quadrivalent inactivated influenza vaccine (Fluzone). Hemagglutination inhibition assays were performed to quantify neutralizing antibodies; functional influenza-reactive CD4 T cells were quantified by flow cytometry, and influenza-specific CD8 T cells were enumerated with MHC Class I tetramers. Antibody seroconversion data were evaluated by Chi-square analysis, and the Mann-Whitney or Wilcoxon signed-rank tests were applied to T cell response data.ResultsPTPN22 R620W carrier (n = 17) and non-carrier (n = 33) groups did not differ in age, parity, BMI, gestational age at time of vaccine, or history of prior influenza vaccination. After Fluzone exposure, 51.5% of non-carriers met criteria for antibody seroconversion to H1N1 influenza, compared with 23.5% of R620W carriers (p = 0.06). Influenza-reactive CD4 T cells showed modest increase at days 9–15 after vaccination in both R620W carriers and non-carriers (p = 0.02 and p = 0.04, respectively). However, there was no difference in overall response between the two groups (p = 0.6). The vaccine did not result in significant induction of influenza-specific CD8 T cells in either group.ConclusionsThere was no significant difference among healthy pregnant R620W carriers and non-carriers in H1N1 antibody seroconversion rates after influenza vaccination. Studies of larger cohorts will be needed to define the effect of PTPN22 risk allele carriage on antibody and T cell responses to influenza vaccination during pregnancy.

Entecavir Combined With Adefovir Ameliorates Patients With Chronic Hepatitis B Who Fail to Respond to Nucleotide (Acid) Analog Monotherapy.

The aim of this study was to evaluate the efficacy and safety of entecavir (ETV) combined treatment with adefovir (ADV) on chronic hepatitic B (CHB) patients who failed to respond to nucleotide (acid) analog (NA) treatment. On this basis, the possible factors in the combined treatment of these patients will be analyzed. The safety, biochemical index, and the possible factors that might affect the ETV and ADV combined treatment at different points in time were retrospectively analyzed. The biochemical index included the following: virological response, hepatitis B virus (HBV) DNA decline, primary nonresponse, biochemical response, and the hepatitis B virus E antigen/hepatitis B virus E antibody seroconversion rate. There were 94 CHB patients and compensated liver cirrhosis patients who received ETV plus ADV treatment for over 12 weeks after failure of treatment with NAs. The authors have also investigated 76 CHB patients (80.9%) and 18 hepatitis B cirrhosis patients (19.1%) in this study. The HBV DNA baseline was 4.4 ± 1.4 log10 IU/mL, and the positive rate of HBeAg before salvage treatment was 78.7% (74/94). The sample sizes were 94, 78, 42, 10, 6, and 1 for follow-up of 24, 48, 96, 144, 192, and 240 weeks, respectively. The virological responses (HBV DNA < 2 log10 IU/mL) and biochemical responses were 52.1%, 74.3%, and 90.4% and 63.1%, 61.6%, and 81.1%, respectively, at 24, 48, and 96 weeks, which showed significant differences (P < 0.001 and P < 0.005, respectively). The HBV DNA decline was presented as mean ± SEM, which were 1.53 ± 1.23, 1.75 ± 1.37, 2.07 ± 1.54, and 2.39 ± 1.77 log10 IU/mL at 12, 24, 48, and 96 weeks, respectively. They showed significant differences compared with the baseline (χ = 8.084, P < 0.05). The rate of primary nonresponse was 30.9% (29/94), and the primary treatment failure rates were 26.6% (25/94), 24.4% (19/78), and 4.8% (2/42) at 24, 48, and 96 weeks, respectively. They all have statistical difference (P = 0.011 < 0.05). There were 23 patients who experienced virological breakthrough after the HBV DNA levels were undetectable, whereas after follow-up for 12-24 weeks, the HBV DNA levels were back to undetectable again. ETV plus ADV treatment is an efficient and safe treatment for CHB and compensated liver cirrhosis patients who experienced NA treatment failure. The high quantity of baseline HBV DNA level is a risk factor for poor efficacy of salvage treatment.