The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.     

Elucidating the difference in the kinetics of antibody titres of infants in Belgium and Vietnam

Serological results obtained in a single laboratory from twin-studies on maternal immunisation, in Vietnam and Belgium offer the opportunity to compare antibody kinetics in infants before and after infant vaccination in the presence of vaccine-induced maternal antibodies. Nonlinear mixed-effects models (NLMMs) making use of a hypothesised dynamic evolution that captures the change in antibody titres over time, were employed to model anti-PT and anti-Prn antibody dynamics. Our proposed modelling approach provided useful insight into understanding the differences in the infants’ antibody kinetics in both countries since NLMMs offer the possibility of pooling all data in one analysis and incorporate relevant covariates of interest.In both controlled cohort studies, pregnant women were vaccinated with a tetanus, diphtheria, acellular pertussis (Tdap) vaccine (Boostrix®, Belgium; Adacel®, Vietnam), and children were followed before and after primary vaccination, and before and after booster vaccination (Infanrix hexa®). From our models, both anti-PRN and anti-PT antibody titres at birth of Vietnamese infants were significantly lower than those of Belgian infants born to vaccinated women groups. Even though the antibody titres in the cord at birth of Belgian infants were also higher than those of Vietnamese infants born to the control women groups, the difference was not significant. The significant difference between infants born to vaccinated women in the two countries was likely due to the use of different vaccine brands in pregnant women and the different vaccination histories of women in these two countries.Our analyses also suggested that the blunting effect was present during the primary immunisation but went away afterward for anti-PT data. In contrast, for anti-PRN antibodies, the blunting effect persisted after the primary vaccination and possibly went away after the booster dose. Countries should be aware of the regional situation in view of recommending maternal immunization.     

Ultrasound biomicroscopy as a tool in the evaluation and management of ocular hypotony in uveitis

Purpose:Chronic uveitis can lead to hypotony that may result in severe visual impairment. We highlight the use of ultrasound biomicroscopy (UBM) as an imaging tool to decide the modality of therapy and management of uveitic hypotony.Methods:This was a retrospective hospital-based interventional case-series study that included a total of 36 eyes of 25 patients with uveitic hypotony seen between January 1997 and January 2020.Results:Thirty-six eyes of 25 patients with uveitic ocular hypotony were included. Unilateral involvement was seen in 56%. The median age of presentation was 21 years with a median follow-up of 21.5 months. Anterior uveitis was noted in 13.88%, intermediate uveitis in 52.77%, and panuveitis in 33.33% eyes. UBM findings commonly noted were pars plana membranes, supraciliary effusion, blunted ciliary process, and ciliary body traction. Other findings included ciliochoroidal detachment and ciliary body edema. Moreover, 22.2% eyes were managed with medical therapy alone, whereas 77.8% eyes received both medical and surgical intervention based on UBM findings. Furthermore, 66.7% eyes showed improvement in intraocular pressure, 13.9% eyes maintained the same IOP, whereas 19.4% eyes had worsening of IOP at final follow-up.Conclusion:We found UBM as a useful imaging tool in evaluating and judiciously deciding the mode of management of uveitic hypotony.     

Enabling bone formation in the aged skeleton via rest-inserted mechanical loading

The mild and moderate physical activity most successfully implemented in the elderly has proven ineffective in augmenting bone mass. We have recently reported that inserting 10 s of unloaded rest between load cycles transformed low-magnitude loading into a potent osteogenic regimen for both adolescent and adult animals. Here, we extended our observations and hypothesized that inserting rest between load cycles will initiate and enhance bone formation in the aged skeleton. Aged female C57BL/6 mice (21.5 months) were subject to 2-week mechanical loading protocols utilizing the noninvasive murine tibia loading device. We tested our hypothesis by examining whether (a) inserting 10 s of rest between low-magnitude load cycles can initiate bone formation in aged mice and (b) whether bone formation response in aged animals can be further enhanced by doubling strain magnitudes, inserting rest between these load cycles, and increasing the number of high-magnitude rest-inserted load cycles. We found that 50 cycles/day of low-magnitude cyclic loading (1200 μ peak strain) did not influence bone formation rates in aged animals. In contrast, inserting 10 s of rest between each of these low-magnitude load cycles was sufficient to initiate and significantly increase periosteal bone formation (fivefold versus intact controls and twofold versus low-magnitude loading). However, otherwise potent strategies of doubling induced strain magnitude (to 2400 μ) and inserting rest (10 s, 20 s) and, lastly, utilizing fivefold the number of high-magnitude rest-inserted load cycles (2400 μ, 250 cycles/day) were not effective in enhancing bone formation beyond that initiated via low-magnitude rest-inserted loading. We conclude that while rest-inserted loading was significantly more osteogenic in aged animals than the corresponding low-magnitude cyclic loading regimen, age-related osteoblastic deficits most likely diminished the ability to optimize this stimulus.     

Pertussis vaccination during pregnancy in Belgium: Results of a prospective controlled cohort study

Vaccination during pregnancy has been recommended in some countries as a means to protect young infants from severe infection. Nevertheless, many aspects are still unknown and possible blunting of the infant's immune responses by maternal antibodies, is one of the concerns with maternal vaccination. We report the first prospective controlled cohort study in women and infants on the effects of using Boostrix^®, a combined tetanus, diphtheria and acellular pertussis vaccine, during pregnancy. The primary aim was to measure the influence of this booster dose on the titer and duration of the presence of maternal antibodies in the infants and assess possible interference with infant immune responses.In a controlled cohort study, 57 pregnant women were vaccinated with Tdap vaccine (Tetanus Diphtheria acellular Pertussis, Boostrix, GSK Biologicals), at a mean gestational age of 28.6 weeks. A control group of pregnant women (N = 42) received no vaccine. Antibody geometric mean concentrations (GMCs) against tetanus (TT), diphtheria (DT), pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (Prn) were measured with commercial ELISA tests in samples taken preceding maternal vaccination and one month afterwards, at delivery and from the cord blood, and in infants before and 1 month after the primary series of 3 pertussis containing hexavalent vaccines.Infants born to vaccinated women had significantly higher GMC at birth and during the first 2 months of life for all vaccine antigens compared to the offspring of unvaccinated women, thereby closing the susceptibility gap for pertussis in infants. However, blunting was noticed for infant diphtheria and pertussis toxin vaccine responses (p < 0.001) in the infants from vaccinated women after the primary vaccination schedule (weeks 8,12 and 16).Since pertussis vaccination has been recommended during pregnancy already, the results of this study support that recommendation and provide additional scientific evidence to document possible interference by maternal antibodies.     

An observational,cohort, multi-centre,open label phase IV extension study comparing preschool DTAP-IPV booster vaccine responses in children whose mothers were randomised to one of two pertussis-containing vaccines or received no pertussis-containing vaccine in pregnancy in England

An antenatal pertussis vaccination programme was introduced in 2012 in the UK in the context of a national outbreak of pertussis. It has been shown that a lower antibody response to primary immunisation can be seen for certain pertussis antigens in infants born to women who received pertussis-containing antenatal vaccines, a phenomenon known as blunting. The longer-term impact of this has not been documented previously, and accordingly was evaluated in this study.Children were predominantly recruited from a previous study in which their mothers had received acellular pertussis-containing antenatal vaccines (dTaP₃-IPV [diphtheria toxoid, tetanus toxoid, three antigen acellular pertussis and inactivated polio] or dTaP₅-IPV [diphtheria toxoid, tetanus toxoid, five antigen acellular pertussis and inactivated polio]), or no pertussis-containing vaccine. Blood samples were obtained prior to and one month after the acellular pertussis-containing preschool booster (dTaP₅-IPV) was given at around age 3 years 4 months. Pre- and post-booster immunoglobulin G (IgG) geometric mean concentrations (GMCs) against pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, and pertactin, were compared.Prior to the receipt of the preschool booster, there was no difference in the IgG GMCs against pertussis-specific antigens between children born to women vaccinated with dTaP₃-IPV and dTaP₅-IPV; however, IgG GMCs against pertussis toxin were significantly lower in children born to women vaccinated with dTaP₃-IPV compared with children born to unvaccinated women (geometric mean ratio 0.42 [95 % CI 0.22–0.78], p = 0.03). One month after the receipt of the preschool booster there was no differences between the groups.The blunting effect of antenatal pertussis vaccine on pertussis responses in children can persist until preschool age, although it is overcome by the administration of a booster dose.ClinicalTrials.gov registration number: NCT03578120     

Abdominal obesity and chronic stress interact to predict blunted cardiovascular reactivity

Abdominal obesity and chronic stress have independent effects on cardiac autonomic regulation, and may also interact to influence cardiovascular reactivity. In addition to main effects, we hypothesized that abdominal obesity and chronic stress would interact and predict blunted cardiovascular reactivity. One hundred and twenty-two undergraduate students engaged in two stressful laboratory tasks while cardiovascular activity was assessed. Results indicated that higher abdominal obesity significantly predicted blunted systolic blood pressure (SBP) and mean arterial pressure (MAP) change, while chronic stress was not directly associated with any measure of cardiovascular reactivity. Furthermore, there was a significant interaction between abdominal obesity and chronic stress on SBP and MAP change such that among participants with higher chronic stress, higher abdominal obesity was significantly associated with reduced SBP and MAP reactivity. In addition, body-mass index (BMI), a measure of overall obesity, also had both main and interaction effects with chronic stress to predict blunted cardiovascular reactivity. These results suggest that abdominally obese individuals may incur difficulty in mounting appropriately-sized cardiovascular responses during acute stress, particularly when under high levels of chronic stress.     

An experimental test of blunting using sleep-restriction as an acute stressor in Type D and non-Type D women

Recent years have seen a growing interest in evidence indicating that a low, or blunted, cardiovascular response to stress may predict increased risk for a range of adverse health outcomes. Type D personality has been associated with poor health in cardiac patients, and more recently, has been associated with lower reactivity to laboratory stress in healthy individuals, underpinned by an increase in vascular responding. Previous findings have also demonstrated that partial sleep restriction is characterised by a robust vascular profile. However, despite the fact that a vascular response profile underpins both reactivity in sleep restricted adults and blunted reactivity in healthy Type D adults, limited empirical work has examined the correlates of sleep restriction and Type D. The present study sought to investigate if manipulation of sleep duration in healthy Type D and non-Type D individuals would alter cardiovascular reactivity to stress, and in particular whether such manipulation could elucidate the comparative nature of blunting. Seventy female university students completed a laboratory social stress task while undergoing continuous hemodynamic monitoring, after either a night of partial sleep restriction or a full night's rest. In both groups, Type D participants exhibited relatively low SBP stress responses, consistent with the view that at-risk groups show blunting in (some indices of) cardiovascular reactivity. For non-Type D participants, low SBP responses were observed only in participants who had undergone sleep restriction, suggesting that sleep-restriction served as an environmental stressor which precipitated in non-Type D persons a cardiovascular stress response resembling that ordinarily seen in Type D persons. This blunted response was associated with an increase in vascular responding. Thus, the findings suggest that blunting is characterised not only by reductions in some (frequently studied) cardiovascular parameters, but also by increases in others.     

Pertussis vaccination during pregnancy in Belgium: Follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age

Vaccination of pregnant women with a pertussis containing vaccine is a recommended strategy in some industrialized countries, to protect young infants from severe disease. One of the effects of the presence of high titers of passively acquired maternal antibodies in young infants is blunting of immune responses to infant vaccination. We present infant immune responses to a fourth pertussis containing vaccine dose at 15 months of age, as a follow-up of previously presented data.In a prospective cohort study, women were either vaccinated with an acellular pertussis vaccine (Boostrix^®) during pregnancy (vaccine group) or received no vaccine (control group).All infants were vaccinated with Infanrix Hexa^® according to the standard Belgian vaccination schedule (8/12/16 weeks, 15 months). We report results from blood samples collected before and 1 month after the fourth vaccine dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT) and diphtheria toxoid (DT) were measured using commercially available ELISA tests. Antibody levels were expressed in International Units per milliliter.Demographic characteristics were similar in the vaccine and control group. Before the fourth vaccine dose, significantly lower antibody titers were measured in the vaccine group compared to the control group for anti-Prn IgG (p = 0.003) and anti-DT IgG (p = 0.023), with a steep decay of antibody titers since post-primary vaccination. One month after the fourth dose, antibody titers were only significantly lower in the vaccine group for anti-PT IgG (p = 0.006). For all antigens, there was a rise in antibody titer after the fourth vaccine dose.The present results indicate still a minor blunting effect 1 month after a fourth vaccine dose for anti-PT antibodies. However, a good humoral immune response on all measured antigens was elicited in both groups of children. The clinical significance of such blunting effect is yet unknown.Clinicaltrials.gov identifier: NCT01698346.