Hepatitis A incidence,seroprevalence, and vaccination decision among MSM in Amsterdam,the Netherlands

BackgroundSeveral outbreaks of Hepatitis A virus (HAV) were recently documented among men who have sex with men (MSM) in Europe. We investigated the HAV incidence among MSM in Amsterdam, the Netherlands; and HAV seroprevalence and HAV vaccination decision among MSM visiting the Sexually Transmitted Infection (STI) clinic in Amsterdam.MethodsUsing surveillance data from 1992 to 2017 of MSM with acute HAV in Amsterdam, we estimated the incidence by calendar year and age. We explored HAV seroprevalence by calendar year and age, determinants for HAV seropositivity, and opting-in/out for HAV vaccination using data collected among MSM that visited the STI clinic between 2006 and 2017 and were included in a nationwide Hepatitis B virus (HBV) vaccination programme. Offering HAV vaccination at the STI clinic differed over three consecutive periods: not offered, offered for free, or offered for 75 euros. Logistic regression analyses were used to explore determinants.ResultsHAV incidence increased in 2016/17 after 4 years of absence and peaked in MSM around 35 years of age. Among MSM visiting the STI clinic, HAV seroprevalence was 37% (95%CI = 35–40%), which was constant over the period 2006–2017, and increased with age (p < 0.001). Determinants for HAV seropositivity in multivariable analysis were: older age (p < 0.001), originating from an HAV endemic country (p < 0.001), and being HBV seropositive (p = 0.001). MSM opted-in more frequently when HAV vaccination was offered for free versus paid (89% versus 11%, respectively; p < 0.001). Younger MSM were less inclined to vaccinate when payment was required (p = 0.010). Post-hoc analyses showed that 98% versus 46% of MSM visiting the Amsterdam STI clinic would be protected against HAV infection if HAV vaccination was offered for free or for 75 euros, respectively.ConclusionsThe MSM population of Amsterdam is vulnerable to a new HAV outbreak. We strongly recommend that MSM have access to free hepatitis A vaccination.     

Skin immunization with third-generation hepatitis B surface antigen using microneedles

L-HBsAg is a third-generation hepatitis vaccine capable of inducing antibodies in non-responders and thus providing potentially therapeutic treatment. In this study, L-HBsAg was administered using microneedles (MN) without an adjuvant to induce intradermal (ID) immunization, and the efficacy of ID immunization was compared with that of intramuscular (IM) immunization that uses a conventional formulation with an adjuvant of aluminum hydroxide (L-HBsAg-AL-IM).The L-HBsAg was dip-coated onto 800-μm-long microneedles made of polylactic acid (PLA). Delivery efficiency and administration time were determined through in vitro experiments using porcine skin. The denaturation of the formulation against sterilization by gamma rays was observed. A storage test and a freeze-thaw cycle test of the microneedles with trehalose as a stabilizer (L-HBsAg-MN-Tre) were observed. An antibody titer of L-HBsAg-MN-Tre was compared with that of the conventional IM immunization of the L-HBsAg solution with aluminum hydroxide (L-HBsAg-AL-IM).The formulation containing L-HBsAg was located on the upper third of the microneedle tips. The formulation on the MN was dissolved and delivered within 30 min of insertion into porcine skin in vitro. Trehalose was selected as a stabilizer, and the stabilizing effect increased with the increase of trehalose content in the solidified formulation. L-HBsAg-MN with 15% of trehalose was stable for 7 days at 40 °C and showed increased stability compared to the conventional liquid formulations. L-HBsAg-MN-Tre showed improved stability during the freeze-thaw cycle. The antibody titer of L-HBsAg-MN-Tre at 28 days was higher than that of L-HBsAg-AL-IM.ID administration of L-HBsAg-MN-Tre showed better efficacy and improved thermal and freeze thaw stability compared to L-HBsAg-AL-IM. Therefore, L-HBsAg-MN-Tre administration showed the possibility of ID delivery of L-HBsAg without the use of an adjuvant for the efficacy, convenience, and safety of pediatric vaccination.     

Uptake of perinatal immunoprophylaxis for infants born to women with a record of hepatitis B in Victoria (2009–2017)

BackgroundMother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains one of the leading causes of transmission worldwide. An estimated 90 % of infants who are exposed to HBV and do not receive appropriate post exposure immunoprophylaxis will go on to develop chronic hepatitis B (CHB). In Australia, universal birth dose vaccination was adopted in 2000 and universal antenatal screening for hepatitis B was introduced in the 1990 s, however up to 10 % of women may have missed screening. There is no coordinated care or data collection that systematically reports the access to interventions to prevent mother-to-child transmission (PMTCT) for women with CHB. Therefore, the incidence rate of MTCT is unknown.MethodsWe conducted retrospective data linkage of perinatal records, public health notification and hospital admission data to identify women with a record of HBV infection who had given birth to a live infant(s) in Victoria between 2009 and 2017. We assessed uptake of birth dose vaccination and hepatitis B immunoglobulin (HBIG) and explored factors associated with administration of birth dose recorded as administered within 7 days.ResultsAmong 690,052 live births, 6118 births (0.90 %) were linked to 4196 women with a record of HBV infection. 89.4 % of all Victorian infants (n = 616,879), and 96.8 % of infants linked to women with a positive record of CHB (n = 5,925) received birth dose within 7 days. Infants born in private hospitals had reduced odds of receiving birth dose when compared to public hospitals births (Victorian population, aOR = 0.67, 95 %CI = 0.66, 0.69; CHB linked records aOR = 0.17, 95 %CI = 0.11, 0.25).Of the 6118 infants linked to a positive maternal record of CHB, discrepant recording of maternal CHB status between the three datasets was identified in 72.4% of records and HBIG administration was recorded for only 2.3% of births.ConclusionAn approach that involves coordinated care and integrates data collection for women with CHB and their infants is required to support the elimination of MTCT of hepatitis B in Victoria.     

Post-vaccination HPV seroprevalence among female sexual health clinic attenders in England

BackgroundThe National HPV Immunisation Programme was introduced in England in September 2008 using the HPV16/18 bivalent vaccine. We conducted serological surveillance to explore vaccination coverage levels. We also conducted a case-control study to investigate a hypothesised cross-protective effect of the HPV16/18 vaccine against genital warts.MethodsResidual serum specimens from 16 to 20 year-old women attending six specialist sexual health services (SSHS) between 2011 and 2015 in England were tested for antibodies against HPV16 and HPV18 using a virus-like particle (VLP)-based multiplex serology assay. Patients were classified as having vaccine-induced seropositivity if they were seropositive for both HPV types and either had high antibody levels for at least one HPV type, or moderately high levels for both HPV types.Differences in vaccine-induced seropositivity by patient characteristics were investigated using logistic regression. Vaccine-induced seropositivity was then compared for patients with genital warts (cases) and matched patients without (controls).ResultsOf 3,973 serum specimens collected, 3,870 (97.4%) had a valid result. The proportion of women with vaccine-induced seropositivity decreased with age (from 78.1% in 16-year-olds to 52.6% in 20-year-olds). Vaccine-induced seropositivity was lower among women born outside the UK, from more deprived areas and with a history of chlamydia diagnosis. A difference in uptake by ethnic group was also seen but this was largely confounded by differences in deprivation and country of birth. Among 537 cases and 1,515 controls, there was little evidence of a protective effect of the bivalent HPV vaccine against genital warts (adjusted odds ratio 0.93; 95% CI: 0.74–1.18).DiscussionVaccine-induced seropositivity in this high-risk population was in line with vaccination coverage in the general population although was lower in some at-risk sub-groups. This study does not provide evidence to support a cross-protective effect of the HPV16/18 vaccine against genital warts.     

Impact of the National Perinatal Hepatitis B Prevention Programme in the Republic of Korea: A retrospective registry-based cohort study

IntroductionHepatitis B is a major preventable cause of morbidity and mortality from chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. We aimed to evaluate the performance and outcomes of the Korean Perinatal Hepatitis B Prevention Programme (PHBPP) and to investigate the impact of the current post-exposure immunoprophylaxis protocol.MethodsA retrospective cohort study was performed based on electronic data registry of infants born to hepatitis B virus (HBV)-infected mothers between July 2002 and 2013.ResultsDuring the study period, 159,983 Korean infants were registered with the PHBPP, with an overall programme coverage of 92.8%. Despite receiving timely post-exposure immunoprophylaxis, 8.6% of infants born to mothers aged <25 years and hepatitis B e antigen (HBeAg)-positive, and 0.7% of infants born to mothers aged ≥25 years and HBeAg-negative were infected. An estimated 14,123 infants were directly protected from perinatal HBV transmission by the PHBPP during the 11.5-year period, at a cost of 1157 US dollars per case averted. The incidence of paediatric hepatocellular carcinoma declined dramatically during the period.ConclusionsA substantial number of infants have been prevented from hepatitis B since the PHBPP was launched in the Republic of Korea. Continued efforts to promote the programme, an integrated approach to maximising its coverage, a risk-stratified strategy, and innovations in logistics could further reduce perinatal HBV transmission.     

Seroprevalence of chronic hepatitis B virus infection and immunity to measles,rubella, tetanus and diphtheria among schoolchildren aged 6–7 years old in the Solomon Islands, 2016

The Western Pacific Region (WPR) established a goal to decrease chronic hepatitis B virus (HBV) infection among children to <1% and to achieve ≥95% hepatitis B vaccine birth dose (HepB-BD) and ≥95% three-dose (HepB3) coverage by 2017. In 2016, we conducted a national serosurvey in the Solomon Islands among 6–7-year-old school children to assess progress towards the control goal and immunity to measles, rubella, tetanus and diphtheria. Eighty schools were selected systematically proportional to their 6–7-year-old population; all 6–7-year-olds were enrolled. We collected basic demographic information and vaccination history. Children were tested for HBV surface antigen (HBsAg) using a rapid test, and for immunity to measles, rubella, tetanus, and diphtheria using a multiplex bead assay. In total, 1,249 out of 1,492 children (84%) were enrolled, among whom 1,169 (94%) underwent HBsAg testing and 1,156 (93%) provided dried blood spots. Almost 80% (n = 982) of enrolled children had vaccination cards, among whom 59% (n = 584) received a timely HepB-BD (within 24 hours of birth), 95% (n = 932) received HepB3, and >90% received vaccines for diphtheria, tetanus, and measles (rubella vaccine was not available at the time). HBsAg prevalence was 3.1% (95% confidence interval (CI): 2.0%–4.9%), with 55% of identified cases from one province. Among 982 children with vaccination cards, HBsAg prevalence was higher among children who had not received a timely HepB-BD and at least two HepB doses compared to those who had (4% vs. 2%). Of 1,156 tested children, immunoprotection estimates were 99% (95% CI: 98%–99%) for measles, 99% (95% CI: 97%–100%) for rubella, 85% (95% CI: 83%–87%) for tetanus, and 51% (95% CI: 47%–55%) for diphtheria. Improving timely HepB-BD coverage and maintaining high HepB3 coverage could help Solomon Islands reach the regional HBV control goal. Low immunity to tetanus and diphtheria suggests the need to introduce booster doses to ensure long-term protection.     

Assessing the impact of the routine childhood hepatitis B immunization program and the need for hepatitis B vaccine birth dose in Sierra Leone, 2018

Sierra Leone is highly endemic for hepatitis B virus (HBV) infection and thus recommends three doses of hepatitis B vaccine (HepB3) from 6 weeks of age but does not recommend a birth dose (HepB-BD) to prevent mother-to-child transmission (MTCT). We evaluated impact of the existing HepB3 schedule and risk for MTCT of HBV. We conducted a community-based serosurvey among 4–30-month-olds, their mothers, and 5–9-year-olds in three districts in Sierra Leone. Participants had an HBV surface antigen (HBsAg) rapid test; all HBsAg-positive and one HBsAg-negative mother per cluster were tested for HBV markers. We collected children’s HepB3 vaccination history. Among 1889 children aged 4–30 months, HepB3 coverage was 85% and 20 (1·3% [95% CI 0·8–2·0]) were HBsAg-positive, of whom 70% had received HepB3. Among 2025 children aged 5–9 years, HepB3 coverage was 77% and 32 (1·6% [1·1–2·3]) were HBsAg-positive, of whom 56% had received HepB3. Of 1776 mothers, 169 (9·8% [8·1–11·7]) were HBsAg-positive. HBsAg prevalence was 5·9% among children of HBsAg-positive mothers compared to 0·7% among children of HBsAg-negative mothers (adjusted OR = 10·6 [2·8–40·8]). HBsAg positivity in children was associated with maternal HBsAg (p = 0·026), HBV e antigen (p < 0·001), and HBV DNA levels ≥ 200 000 IU/mL (p < 0·001). HBsAg prevalence was lower among children than mothers, for whom HepB was not available, suggesting routine infant HepB vaccination has lowered HBV burden. Since HBsAg positivity in children was strongly associated with maternal HBV infection and most of the HBsAg-positive children in the survey received HepB3, HepB-BD may prevent MTCT and chronic HBV infection.     

Response to hepatitis B vaccination is co-determined by HLA-DPA1 and -DPB1

Background and aimsNo report explored the combined effects of HLA-DPA1 and -DPB1 with long-term response to hepatitis B (HB) vaccination (HBVac). The specific aims of the study were to assess the combined effects and relative contributions of DPA1 and DPB1 genes.MethodsThe cases were 152 adolescents who had undetectable (<1.0 mIU/mL) post-booster anti-HBs titers and the controls were adolescents who had residual anti-HBs ≥ 10 mIU/mL at aged 16 years (n = 207) or had detectable (≥1.0 mIU/mL) anti-HBs titers after booster HBVac (n = 481). HLA-DPA1 and -DPB1 genotypes were determined by sequence-based typing.ResultsHLA-DPA1*01:03:01 was correlated with lower ORs of undetectable anti-HBs titers, while -DPA1*02:02:02 and -DPB1*05:01:01 were correlated with higher ORs. The ORs for HLA-DPA1*01:03:01-DPB1*05:01:01 and DPA1*02:02:02-DPB1*protective combinatory types were significantly less than 1.0. As compared with subjects who had no protective allele, the adjusted ORs (95% CI) were 0.545 (0.328–0.906), 0.350 (0.174–0.702), and 0.122 (0.058–0.257), for subjects who had protective alleles on DPA1only, DPB1 only, and both genes, respectively. Analyses of amino acid polymorphisms showed that subjects who carried Arg81-Pro158-Val191-Pro259α + Met234β and Gln62-Arg82α + Met234β combinations had 4.3-to-4.6 folds of risks.ConclusionBoth DPA1 and DPB1 genes contribute to the persistence of immunological response to primary infantile HBVac. The effects of HLA-DP risk alleles were dominated by the protective alleles and there were significant gene-gene interactions. Our findings provide evidences for the design of more potent HB vaccine.     

Human papillomavirus vaccination coverage among men who have sex with men—National HIV Behavioral Surveillance,United States, 2017

Men who have sex with men (MSM) are at high risk for infections and diseases caused by human papillomavirus (HPV), many of which are vaccine-preventable. In the United States, routine HPV vaccination has been recommended for adolescent males since 2011. This analysis evaluated self-reported receipt of ≥ 1 HPV vaccine dose by age group and HIV status among adult MSM using 2017 data from National HIV Behavioral Surveillance (NHBS) and compared the proportion vaccinated to prior years. Among 10,381 MSM aged ≥ 18 years, 17.9% of MSM overall and 28.4% of MSM living with HIV reported any HPV vaccination. Among 2,482 MSM aged 18–26 years, 32.8% overall and 51.3% living with HIV reported HPV vaccination. Since 2011, the proportion of MSM aged 18–26 years reporting HPV vaccination has increased over six-fold. As vaccinated adolescents age into young adults, coverage will continue to increase overall, including among MSM.     

The impact of the COVID-19 pandemic on hepatitis B virus vaccination and transmission among men who have sex with men: A mathematical modelling study

BackgroundDuring the COVID-19 pandemic, the number of hepatitis B virus (HBV) vaccinations among men who have sex with men (MSM) has been considerably lower than before the pandemic. Moreover, less frequent HBV testing and a reduction in numbers of sex partners have been reported. We assessed the impact of these COVID-19-related changes on HBV transmission among MSM in the Netherlands.MethodsWe estimated the changes in sexual activity, HBV testing, and HBV vaccination among MSM during the pandemic from Dutch data. We used a deterministic compartmental model and investigated scenarios with small or large declines in sexual activity, testing, and vaccination for the current phase of the pandemic (without available data). We examined the increase in HBV vaccinations needed to prevent further increase in HBV incidence.ResultsWith a decrease in numbers of sex partners of 15–25% during the first lockdown and 5% during the second lockdown, we found a decline of 6.6% in HBV incidence in 2020, despite a >70% reduction in HBV testing and vaccination during the first lockdown. With numbers of sex partners rebounding close to pre-pandemic level in 2021, and a reduction of 15% in testing and 30% in vaccination in 2021, we found an increase of 1.4% in incidence in 2021 and 3.1% in 2026. With these changes, an increase of ≥60% in HBV vaccinations in 2022 would be needed to bring the HBV incidence in 2023 back to the level that it would have had if the COVID-19-related changes had not occurred.ConclusionsDespite reductions in sexual activity during the COVID-19 pandemic, the decrease in HBV vaccinations may result in a small increase in HBV incidence after 2021, which may persist for years. It is important to restore the vaccination level and limit further increase in HBV transmission among MSM.     

Influenza vaccination coverage among adults with diabetes,United States, 2007–08 through 2017–18 seasons

BackgroundDiabetes is associated with higher risk of hospitalization, morbidity, and mortality from influenza. We assessed influenza vaccination coverage among adults aged ≥ 18 years with diabetes during the 2007–08 through 2017–18 influenza seasons and identified factors independently associated with vaccination during the 2017–18 season.MethodsWe analyzed data from the 2007–2018 National Health Interview Surveys, using Kaplan-Meier survival analysis to estimate season-specific influenza vaccination coverage. Multivariate logistic regression was conducted to examine whether diabetes was independently associated with self-reported influenza vaccination in the past 12 months and identify factors independently associated with vaccination among adults with diabetes using the 2017–18 data.ResultsDuring the 2007–08 through 2017–18 influenza seasons, influenza vaccination coverage among adults aged ≥ 18 years with diabetes ranged from 62.6% to 64.8%. In the 2017–18 influenza season, coverage was significantly higher among adults with diabetes (64.8%) compared with those without diabetes (43.9%). Having diabetes was independently associated with an increased prevalence of vaccination after controlling for other factors. Among adults with diabetes, living at or above poverty level, having more physician contacts, having usual place for health care, and being unemployed were independently associated with increased prevalence of vaccination; being 18–64 years and non-Hispanic black were independently associated with decreased prevalence of vaccination.ConclusionsDespite specific recommendations for influenza vaccination among people with diabetes, more than one-third of adults with diabetes are unvaccinated. Targeted efforts are needed to increase influenza vaccination coverage among adults with diabetes.     

Influenza vaccination and respiratory virus interference among Department of Defense personnel during the 2017–2018 influenza season

PurposeReceiving influenza vaccination may increase the risk of other respiratory viruses, a phenomenon known as virus interference. Test-negative study designs are often utilized to calculate influenza vaccine effectiveness. The virus interference phenomenon goes against the basic assumption of the test-negative vaccine effectiveness study that vaccination does not change the risk of infection with other respiratory illness, thus potentially biasing vaccine effectiveness results in the positive direction. This study aimed to investigate virus interference by comparing respiratory virus status among Department of Defense personnel based on their influenza vaccination status. Furthermore, individual respiratory viruses and their association with influenza vaccination were examined.ResultsWe compared vaccination status of 2880 people with non-influenza respiratory viruses to 3240 people with pan-negative results. Comparing vaccinated to non-vaccinated patients, the adjusted odds ratio for non-flu viruses was 0.97 (95% confidence interval (CI): 0.86, 1.09; p = 0.60). Additionally, the vaccination status of 3349 cases of influenza were compared to three different control groups: all controls (N = 6120), non-influenza positive controls (N = 2880), and pan-negative controls (N = 3240). The adjusted ORs for the comparisons among the three control groups did not vary much (range: 0.46–0.51).ConclusionsReceipt of influenza vaccination was not associated with virus interference among our population. Examining virus interference by specific respiratory viruses showed mixed results. Vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus; however, significant protection with vaccination was associated not only with most influenza viruses, but also parainfluenza, RSV, and non-influenza virus coinfections.     

Variable anti-HBs antibody titers in vaccinated birth cohorts – A cross-sectional population-based study

BackgroundAfter the introduction of hepatitis B (HB) vaccination in 1995 in newborns, two catch-up campaigns targeted unvaccinated 9 year old in 2000–2003 (born 1991–1994) and the 18 year old in 2004–2008 (born 1986–1990), resulting in several birth-cohorts. Our objective was to assess the anti-HBs titers in each birth-cohort.MethodsWe included all outpatients (78.5%) and hospitalized patients with measured anti-HBs antibody titers in the Teaching Hospital of Infectious Diseases, Cluj-Napoca, Romania, during April 2014 – December 2018 (without HB history). We compared the anti-HBs titers in all birth-cohorts using the Lexis surfaces (titers by age, time period and cohort patterns). We also evaluated the number of acute HB in the corresponding inpatient birth-cohorts and special groups.ResultsWe included 2963 participants, mean age = 31.0 ± 14.2, 64.1% women. The birth-cohort 1995–2006, vaccinated after delivery (n = 424, 3-dose HB vaccine coverage > 90%), had significantly lower protective titers (41.3% >10 mIU/mL) compared to the other birth-cohorts: born after 2007 (also vaccinated at birth, 67.0%, n = 106), 1991–1994 (age 9, 74.3%, n = 847), 1986–1990 (age 18, 71.3%, n = 543). In the unvaccinated cohort (n = 1043, mean age = 45.5 ± 12.4) protective titers were found in 44.8%, probably after self-limited HB infection.Concordant results were found using the proportion of patients with detectable or robust titers, and median or geometric mean titers.Four breakthrough acute HB infections were hospitalized of the corresponding vaccinated cohorts (birth years 1988, 1990, 1995, 1996). Data on a few tested infants (n = 47, not included in the main study) demonstrated good protection, 88.9%.ConclusionsOur study demonstrated the long-term evidence of protection of HBV vaccine at two decades following the primary immunization and a booster seems unsupported. Further studies should be done to assess the need of a booster dose within the general population and special groups.     

Increasing seroprevalence but waning herd immunity against measles after elimination: Longitudinal seroepidemiology of measles in Osaka Prefecture,Japan, 2003–2020

Japan is one of the countries conducting longitudinal serosurveillance of vaccine-preventable diseases. We conducted surveillance of the local measles-specific antibody titer, calculated the effective reproduction number (R_e), and compared data of four terms: term 1, 2003–2006 (before the introduction of the second shot of measles-containing vaccine); term 2, 2007–2010 (early term toward measles elimination); term 3, 2011–2014 (later term toward measles elimination); and term 4, 2015–2020 (after elimination of measles in Japan). Approximately 250 sera from volunteers aged 0 to ≥ 40 years were collected and examined for measles-specific IgG using the gelatin particle agglutination (PA) method annually from 2003 to 2020. Seroprevalence and the geometric mean of the PA antibody titer were examined by term. R_e was calculated using the age-dependent proportion immune and contact matrix for each term. Of the 4,716 sera, 886 in term 1, 1,217 in term 2, 1,069 in term 3, and 1,544 in term 4 were collected. The seroprevalence gradually increased from term 1 (88.3% CI 86.0–90.3) to term 4 (95.7% CI 94.6–96.7), and the seroprevalence of term 1 was significantly lower than those of other terms (Fisher’s exact test, p < 0.001), with PA titer ≥ 16 as positive. By contrast, PA antibody titers significantly decreased from term 1 (median 1,024) to term 4 (median 256) (Mann–Whitney U test, p < 0.001). With the protection level (PA titer ≥ 128 and ≥ 256) as positive, R_e gradually increased from term 1 (1.8 and 2.3) to term 4 (2.5 and 4.8, respectively). Waning levels of measles antibodies potentially increase the measles susceptibility in Osaka, Japan. This trend might imply a limitation of vaccine-induced immunity in the absence of a natural booster for wild strains after measles elimination. This study provides a cue for maintaining continuous measles elimination status in the future.     

The C-terminal region of the Plasmodium yoelii microgamete surface antigen PyMiGS induces potent anti-malarial transmission-blocking immunity in mice

Malaria transmission-blocking vaccines (TBVs) aim to inhibit parasite fertilization or further development within the mosquito midgut. Because TBV-immunized individuals reduce the transmission of malaria parasites to mosquito vectors, TBVs could serve as a promising strategy to eliminate malaria. We previously reported that a male specific protein, PyMiGS (Plasmodium yoelii microgamete surface protein), is localized to the surface of microgametes and anti-PyMiGS antibodies have strong transmission-blocking activity. In this study we determine a region of PyMiGS that contains epitopes inducing potent transmission-blocking antibodies. PyMiGS excluding the N-terminal signal sequence and C-terminal hydrophobic region (PyMiGS-full) was divided into five overlapping regions, named I through V, and corresponding truncated recombinant proteins were produced. Anti-region V antibody, affinity-purified from anti-PyMiGS-full rabbit antiserum, significantly reduced the number of oocysts in a mosquito membrane-feeding assay. Antibodies from mice immunized with PyMiGS-V recognized the microgamete surface and showed higher transmission-blocking efficacy than antibodies obtained by PyMiGS-full immunization. These results indicate that the major epitopes for transmission-blocking antibodies are within region V at the C-terminal region of PyMiGS. Therefore, region V of MiGS could be a promising pre-fertilization TBV candidate antigen.     

Booster immunization improves the generation of T follicular helper (Tfh) cells specific to hepatitis B surface antigen (HBsAg) after prenatal HBsAg exposure

Breakthrough infections of hepatitis B virus (HBV) after neonatal vaccination occurred in some adolescents and young adults who were born to mothers with hepatitis B surface antigen (HBsAg). We aimed to determine the impacts of prenatal HBsAg exposure on the generation of T follicular helper (Tfh) cells and antibodies (anti-HBs) specific to HBsAg. To mimic human prenatal HBsAg exposure, we mated female Alb1-HBV (HBV-M) mice with male C57BL/6J mice. Of their first filial generation (F1), HBV-M/F1⁺ expressed HBsAg in liver tissues and blood, and HBV-M/F1⁻ mice exposed HBsAg in amniotic fluid. At their four weeks old, each HBV-M/F1 mouse was immunized with hepatitis B vaccine containing 5 μg HBsAg subcutaneously. Both HBV-M/F1⁻ and HBV-M/F1⁺ mice had reduced generation of HBsAg-specific CD4⁺CXCR5⁺PD1⁺ Tfh cells and CD138⁺IgD⁻ plasma cells in comparison with C57BL/6J mice. Results of coculturing the Tfh cells with B cells that were isolated from different strains of mice indicated that CD4⁺ T cell activation in response to HBsAg was critical for anti-HBs generation after prenatal HBsAg exposure. When interleukin (IL) 21 was supplemented, the generation of HBsAg-specific Tfh and plasma cells in HBV-M/F1⁻ mice was improved, while supplementation showed little effect in HBV-M/F1⁺ mice. In HBV-M/F1⁻ mice, HBV vaccine booster improved the generation of Tfh cells and plasma cells, and enhanced anti-HBs production.ConclusionImpaired generation of HBsAg-specific Tfh cells and plasma cells after prenatal HBsAg exposure can be improved by HBV vaccine booster, most likely increasing IL-21 production.     

Kinetics of pneumococcal antibodies among HIV-exposed,uninfected infants in Botswana

BackgroundStreptococcus pneumoniae is a leading cause of severe infections among children. Despite vaccination, HIV-exposed, uninfected (HEU) children have a higher incidence of invasive pneumococcal disease than HIV-unexposed, uninfected (HUU) children. We sought to compare the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV-13) in HEU and HUU infants.MethodsWe conducted a prospective cohort study of 134 mother-infant dyads in Botswana. Infants received PCV-13 doses at 2, 3, and 4 months through routine clinical care. We measured IgG antibodies specific to vaccine serotypes in sera collected from infants at 0, 5, and 12 months of age. We calculated the proportion of infants with protective IgG levels (≥0.35 µg/mL) to specific pneumococcal serotypes.ResultsAt birth, fewer than half of infants had protective IgG levels to serotypes 1 (38%), 3 (46%), 4 (33%), 5 (23%), 6B (40%), 7F (44%), 9 V (44%), and 23F (46%). Compared to HUU infants (n = 97), HEU infants (n = 37) had lower antibody concentrations at birth to serotypes 5 (p = 0.046) and 19A (p = 0.008) after adjustment for maternal age and infant birth weight. More than 80% of HEU and HUU infants developed protective antibody levels to each of the 13 vaccine serotypes following PCV-13 vaccination. Median concentrations of antibodies to pneumococcal serotypes declined by 55–93% between 5 and 12 months of age, with fewer than half of infants having protective antibody levels to serotypes 1 (47%), 3 (28%), 9 V (44%), 18C (24%), and 23F (49%) at 12 months of age.ConclusionsBoth HEU and HUU infants developed protective antibody responses to PCV-13 administered in a 3 + 0 schedule. However, antibody concentrations to many pneumococcal serotypes waned substantially by 12 months of age, suggesting that a PCV-13 booster dose in the second year of life may be needed to maintain protective pneumococcal antibody levels in older infants and young children.     

Syngeneic B16-F1 cells are more efficient than allogeneic Cloudman cells as antigen source in DC-based vaccination in the B16-F1 murine melanoma model

A major obstacle to obtaining relevant results in cancer vaccination has been the lack of identification of immunogenic antigens. Dendritic cell (DC)-based cancer vaccines used preventively may afford protection against tumor inoculation, but the effect of antigen choice on anti-tumor protection is not clear. When using irradiated syngeneic tumor cells to load DCs, tumor self-antigens are provided, including tumor-associated antigens (TAAs) and neoantigens generated by tumor mutations. On the other hand, allogeneic tumor cells could only supply shared TAAs. To assess the advantages of each source in protective vaccination, we analyzed in C57BL/6 mice the effect of loading DCs with irradiated syngeneic B16-F1 or allogeneic Cloudman melanoma cells; both cell lines were characterized by whole exome sequencing and RNAseq. Tumor cell components from the two irradiated cell lines were efficiently internalized by DCs, and transported to MHC-class II positive tubulovesicular compartments (MIICs). DCs loaded with allogeneic irradiated Cloudman cells (DC-ApoNec_ALLO) induced a partially effective anti-melanoma protection, although Cloudman and B16-F1 cells share the expression of melanocyte differentiation antigens (MDAs), cancer-testis antigens (CTAs) and other TAAs. DCs loaded with syngeneic B16-F1 cells (DC-ApoNec_SYN) established a more potent and long-lasting protection and induced a humoral anti-B16F1 response, thus suggesting that neoepitopes are needed for inducing long-lasting protection.     

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay

Objective(s)In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017.MethodsS. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)].Results11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP.Conclusion(s)Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.     

Influenza vaccination uptake among high-risk target groups and health care workers in Spain and change from 2017 to 2020

ObjectiveUsing the 2020 European Health Survey for Spain (EHSS2020), which ran from July 2019 to July 2020, we aimed to describe influenza vaccination uptake among the following target groups; individuals aged ≥65 years, health care workers (HCWs), and persons with high-risk chronic medical conditions. We analyzed changes in uptake since the previous Spanish National Health Interview Survey conducted in 2017 and identified variables associated with vaccine uptake.MethodsWe performed a cross-sectional study. The primary study variable was the self-reported uptake of influenza vaccine in the previous year. We analyzed sex, age, country of birth, and being an HCW. We identified participants with self-reported respiratory diseases, cardiovascular disease, diabetes, cancer, and cerebrovascular diseases. Multivariable logistic regression was applied to assess changes over time and to identify variables associated with vaccination in target groups.ResultsUptake was 19.2% in 22,072 participants aged ≥15 years. Uptake was 54.4% for those aged ≥65 years, 41.6% for those with a high-risk medical condition, and 26.53% among HCWs. Uptake by disease was 52.1% for cerebrovascular diseases, 51.3% for cardiovascular diseases, 48.3% for diabetes, 46.1% for cancer, and 36.2% for respiratory diseases. No significant improvement has been observed since 2017 in any target group, except for participants with cancer, whose uptake increased from 33.2% to 46.1%(p < 0.001).The variables that significantly increased the probability of reporting vaccine uptake were female sex, age ≥35 years, being born in Spain, self-reported respiratory or cardiovascular diseases, diabetes, cancer, and being a HCW.ConclusionsInfluenza vaccination uptake among target groups in Spain is below desirable levels and has not improved significantly since 2017. Older age, female sex, and being born in Spain are positive predictors of vaccine uptake.The COVID-19 pandemic highlights the urgent need to implement new strategies to increase influenza vaccine uptake.