High Maternal Antibody Titres Research Articles

Successful management of severe Kell alloimmunization in pregnancy with intravenous immune globulin

Hemolytic Disease of the Fetus and Newborn (HDFN) is a condition that affects 1 to 2 out of 1000 patients during pregnancy (1). When an alloantibody is present, it is essential to identify its nature in order to organize appropriate follow-up. Kell-mediated HDFN is rare; it occurs in about 5% of Kell alloimmunized pregnant women. It is important to note that in case of anti-Kell immunization, the severity of HDFN is not correlated with maternal antibody titers, and anemia tends to occur earlier and more severely. Therefore, early diagnosing and management of this condition is crucial. In the management of severe fetal anemia due to Kell immunization, available treatments include in utero transfusion (IUT), immunoglobulin therapy. Other alternative treatments exist, such as plasmapheresis. Intravenous immunoglobulin (IVIG), a noninvasive therapeutic approach, acts through multiple mechanisms. IVIG has been evaluated in cases of RhD immunization with high maternal antibody titers and a history of pregnancies involving early hydrops or intrauterine death. Regarding the potential benefits of intravenous IgG therapy, it may delay the need for early IUT, reduce the overall reliance on IUT, and have a positive impact on obstetric outcomes. This case of IV IgG therapy of anti-Kell immunization offers a thought-provoking avenue for future exploration.

Antitetanus toxoid antibodies in mothers and neonates: a single-centre study from Uganda

BackgroundNeonatal mortality due to tetanus persists in Uganda despite the mandatory vaccination of pregnant mothers. Maternal antibodies wane within a year. Uganda’s maternal vaccination guidelines do not specify the timing...

The ability to resist Newcastle disease through inherited immunity in different strains of broilers in Nineveh governorate.

Newcastle disease (ND) is a viral disease that affects numerous bird species and is still present in many places, including Iraq. The purpose of this study was to compare maternal derived antibodies against against ND vaccination in 1-day-old imported Cobb 500 and Ross 308 chicks. From April to October 2020, four locations in Mosul governorate were chosen to compute the maternal derived antibodies from 1-day-old broiler chicks. Seven hundred and seven blood samples (451) from imported 28 Ross 308 flocks and 256 from 17 Cobb 500 flocks were obtained and tested for antibody levels using an indirect enzyme-linked immunosorbent assay assay (BioChek commercial kit, UK). The Cobb 500 broiler chicks outperformed the Ross 308 broiler chicks in that all of the Cobb 500 broiler chicks had maternal antibody titers (100% positivity) versus 97.78% of the Ross 308 chicks, had a mean Maternal antibody titer of 9,871.47 versus 8,647.76, and had a mean CV percentage of 12.41% versus 15.18%, respectively. The mean vaccination index of Cobb 500 broiler chicks was 966.59 versus 821.60 for Ross 308 broiler chicks. Although both broiler types produced chicks with high and uniform maternal antibody titers, Cobb 500 produced chicks with higher protective titers than Ross 308.

Maternal Immunization: Nature Meets Nurture.

Vaccinating women in pregnancy (i.e., maternal immunization) has emerged as a promising tool to tackle infant morbidity and mortality worldwide. This approach nurtures a ‘gift of nature,’ whereby antibody is transferred from mother to fetus transplacentally during pregnancy, or postnatally in breast milk, thereby providing passive, antigen-specific protection against infections in the first few months of life, a period of increased immune vulnerability for the infant. In this review, we briefly summarize the rationale for maternal immunization programs and the landscape of vaccines currently in use or in the pipeline. We then direct the focus to the underlying biological phenomena, including the main mechanisms by which maternally derived antibody is transferred efficiently to the infant, at the placental interface or in breast milk; important research models and methodological approaches to interrogate these processes, particularly in the context of recent advances in systems vaccinology; the potential biological and clinical impact of high maternal antibody titres on neonatal ontogeny and subsequent infant vaccine responses; and key vaccine- and host-related factors influencing the maternal-infant dyad across different environments. Finally, we outline important gaps in knowledge and suggest future avenues of research on this topic, proposing potential strategies to ensure optimal testing, delivery and implementation of maternal vaccination programs worldwide.

Effect of Parenteral Vaccination of Newborn Holstein Calves against Viral Agents Involved in Bovine Respiratory Disease (BRD)

Background: Newborn calves are born immunosuppressed, hypogammaglobulinemic, immunologically immature, and therefore more vulnerable to many infectious diseases. During pregnancy, the fetal-placental environment is regulated by Th2-type cytokines that neutralize Th1 responses, an important factor for immune defense against viral agents. The ingestion and absorption of colostral immunoglobulins enhance the immunity of the neonate. However, the presence of maternal antibodies might negatively affect the success of parental vaccination in the first two months of life. This study aimed to evaluate the effecacy of parenteral vaccination in newborn calves with high titers of maternal antibodies against respiratory viruses.Materials, Methods & Results: Twenty-eight Holstein calves were allocated to the vaccinated group (VAC, n = 18) or an unvaccinated control group (NVAC, n = 10). The initial vaccination with 5 mL of a commercial vaccine occurred around the 14th day of life (D14) and the booster at D35. Respiratory and diarrhea symptoms were evaluated at D12, D14, D16, D20, D31, D36, D45, D53, and D60. Blood samples were taken for leukogram, haptoglobin, and seroneutralization of BVDV, BoHV-1, BRSV, and BPI3V, at the time of vaccination at D14 (T1), at booster (D35, T2), and 21 days after the booster (D56, T3). Despite the increased prevalence of BRD during the period of the study, no calves from either group exhibited respiratory disease at D12 or D14. In subsequent assessments, the frequency of BRD increased over time in the VAC group until it reached a maximum prevalence of 38.9% (7/18) at D31. In the NVAC group, the maximum prevalence observed was 40% at D45 and D60. A comparison of the frequencies for BRD cases showed a statistical trend at D36 (P = 0.07), with a higher prevalence for the NVAC group (30%) in relation to the VAC group (5.6%). For the NVAC group, a greater number of total leukocytes was observed at T3 (P = 0.038) and granulocytes (trend) at T2 (P = 0.066). Time analysis demonstrated a decrease in haptoglobin concentration in both groups (NVAC, P = 0.005 and VAC, P = 0.006), with a reduction in the values at T1 and T3 (NVAC = 0.005 and VAC = 0.024). Antibody titers were similar between groups for BVDV, BoHV-1, and BRSV. Higher titers for BPI3V were observed for the VAC group at D56 (P = 0.045).Discussion: The early-onset BRD was present in both groups between 30 and 60 days of age, based on the higher prevalence observed. These data reinforce the importance of early immunization programmes before infection. Factors such as management practices and facilities may have also contributed to the higher prevalence of BRD. The increased number of leukocytes and neutrophils at T2 (D35) and T3 (D56) in the NVAC group points to a stronger inflammatory response to various types of potential challenges. The inflammatory leukocyte profile explains the higher haptoglobin values observed in the NVAC group at T2 (D35). The similarity of titers of antibodies against BVDV, BoHV-1, and BRSV between groups may indicate that vaccinating the calves at 14 days of age did not induce a humoral immune response to these viruses, likely due to interference from the maternal antibodies. Early vaccination prevented a drop in specific viral antibodies and promoted partial protection for vaccinated calves around 14 days of age, with a decrease in the intensity of the inflammatory response at the peak of the disease and a higher concentration of antibodies against BPI3V after the booster.

Respiratory Syncytial Virus Vaccines: Are We Making Progress?

Respiratory Syncytial Virus Vaccines: Are We Making Progress?

Effect of maternal antibody on the infant immune response to inactivated poliovirus vaccines made from Sabin strains

ABSTRACTThis study aimed to evaluate the effect of maternally derived antibody on the immunogenicity of Sabin IPV. A total of 600 infants were randomized to receive one of the five different vaccines: the high- (group A), medium- (group B) or low-dose (group C) of investigational Sabin IPV, the control Salk IPV (group D) or the control Sabin IPV (group E), at 2, 3 and 4 months of age. The post-vaccination GMTs, GMIs and seroconversion rates of poliovirus type–specific neutralizing antibody were analyzed for different maternal antibody levels. The correlations between maternal antibody levels and post-vaccination antibody responses were also modeled by linear regressions. The post-vaccination GMTs were significantly lower among infants with high maternal antibody titers for poliovirus type 1 or 2 mainly in the groups B, C, D and E. The GMIs and seroconversion rates decreased significantly with the increase of maternal antibody levels in all the five groups. In the groups A, B and C, maternal antibody levels were negatively associated with the post-vaccination antibody titers (for poliovirus type 1 and 2) and the fold increases of post-vaccination antibody (for all the 3 poliovirus types). With the reduce of potency of the investigational Sabin IPVs, the linear regression coefficients increased accordingly in the groups A, B and C. In conclusion, high levels of maternal poliovirus antibody could attenuate the immune responses to the Sabin IPVs. Altering the potency of the investigational Sabin IPVs could alter the associations between maternal antibody levels and the serologic responses of infants.

Gumboro disease (IBD)

Gumboro Disease (IBD) caused by Infectious Bursal Disease Virus is an immunosuppressive condition of chickens, which resulted in severe economical losses. Approximately 47 years after the first appearance of the disease, the changes in the form of presentation and pathogenicity of IBDV in the field has resulted in continual changes and adjustments of the vaccines used to control IBD. The original form of the disease, also known as classic or clinical IBD, was usually observed after the third week of life with high mortality, depending on factors, such as virulence of the strain of virus involved, age of the birds and maternal antibody status. The acute IBD is caused by the very virulent IBDV strains, characterized by high mortality rates in vaccinated chickens and the clinical signs and lesions are similar to those of the classic form. The subclinicalform of the disease is associated with the "variant" strains of IBDV and is characterized by low mortality and severe immunosuppression. Initially, the classic IBD was controlled by the use of mild vaccines produced in the early 1970s and from the late 1980s revealed absence of protection from wIBDV in vaccinated chickens. Another group of vaccinal strains, known as intermediate plus vaccine, has been used to control wIBDV strains. These vaccines multiply in birds, even in the presence of high maternal antibody titers. In the USA and other countries, the disease from the variant strains was controlled by intermediate strains as well as by inactivated vaccines that included variant strains, thus providing maternal antibodies against both the standard and variant strains. Until today, the IBD continues to pose an important threat to commercial poultry industry. The high resistence of IBDV to physical and chemical agents accounts for persistence of the virus in the outside environment, particularly on contaminated farms, despite disinfection. Nevertheless and not quite unexpected for the IBDV mutations in the genome, resulted in the emergence of antigenic variant strains in vaccinated flocks. The IBD requires heightened vigilance and the incidence and prevalence of the clinical and immunosuppressive forms must be evaluated more precisely.

Pertussis vaccination in pregnancy: State of the art.

Pertussis vaccination in pregnancy has been introduced by several national advisory bodies, mostly in industrialized countries, as a means to protect young infants from disease by high titers of maternal antibodies. Most recommendations derive from epidemiological needs, but many knowledge gaps remained after implementation. This report aims to overview the solved and unsolved aspects of prenatal vaccination with a pertussis containing vaccine.

Longitudinal monitoring for respiratory pathogens in broiler chickens reveals co-infection of Chlamydia psittaci and Ornithobacterium rhinotracheale.

Chlamydia psittaci is prevalent in broiler chicken production. However, the role of C. psittaci in the respiratory disease complex needs to be clarified. Our aim was to identify the time point when a C. psittaci infection appeared on a broiler farm and to examine the presence of other respiratory pathogens at that time. We focused on the 'major' respiratory pathogens occurring in Belgian broilers, namely infectious bronchitis virus (IBV), avian metapneumovirus (aMPV), Ornithobacterium rhinotracheale, Mycoplasma gallisepticum and Mycoplasma synoviae, and examined their co-occurrence with C. psittaci on three commercial broiler farms. For all farms, 1-day-old broilers showed high maternal antibody titres against C. psittaci in the presence of viable C. psittaci. Maternal antibodies seemed to protect against respiratory signs. Maternal antibodies declined and clinical outbreaks could be identified serologically even before maternal antibodies completely disappeared. Mixed infections with genotypes B/C and B/C/D were observed. Broilers with C. psittaci antibody increases showed conjunctivitis, signs of upper respiratory disease and dyspnoea. C. psittaci always preceded an O. rhinotracheale infection. Infections with aMPV, IBV or Mycoplasma spp. were not observed. Evidence was provided that C. psittaci could occur at an early age in broilers without a predisposing respiratory infection. Both C. psittaci and O. rhinotracheale should be considered when developing prevention strategies for respiratory disease in broilers.

Research of immune response in unvaccinated piglets against porcine circovirus type 2

Infection of pigs caused by porcine circovirus type 2 (PCV2) is present throughout the world. The aim of this study was to determine, based on the follow-up of the class IgG titers in piglets and fattening pigs, the duration of colostral immunity against infections in pigs caused by PCV2. The study included 28 piglets, whose titer was determined by using indirect ELISA test in intervals up to 110 days of age. The observed average values of IgG in piglets aged 21 days (8.47 log2) and 35 days (6.69 log2) in our surveys indicate very high titers of maternal antibodies, and that the piglets at this age are, to some extent, protected from infection caused by PCV2. Absence of the specific anti PCV2 antibodies was determined in 14.29% (21 days old) and 15.38% (35 days old) piglets at this age. The average titer of antibodies, specific for PCV2, in blood serum of piglets on the 50th day decreased to 3.74 log2, what indicates that in the majority of piglets (61.54%) catabolism of colostral antibodies occurred. On the 80th day of the piglets life there were no seropositive specimens, which unambiguously indicates that in this age, there was a complete catabolism of colostral antibodies and the disappearance of passive immunity. In all the 110 days? old fattening pigs, an average antibody titer recorded a sharp rise (12.78 log2). Possible reasons for this sudden increase in PCV2 antibody titers in the blood serum of fattening pigs is is a widespread presence of this infection in our region, as well as the fact that there exists a part of pigs population which is not immune to PCV2 infection. The results of this research are important for choosing the optimal moment for vaccination, considering that high titers of colostral antibodies of class G on the 21st and 35th day of piglets? life have been proven. This data points out to a possible interference with vaccine immunogens in the case of vaccination in this particular age.

Maternal immunity against avian influenza H5N1 in chickens: limited protection and interference with vaccine efficacy

After avian influenza (AI) vaccination, hens will produce progeny chickens with maternally derived AI-specific antibodies. In the present study we examined the effect of maternal immunity in young chickens on the protection against highly pathogenic AI H5N1 virus infection and on the effectiveness of AI vaccination. The mean haemagglutination inhibition antibody titre in sera of 14-day-old progeny chickens was approximately eight-fold lower than the mean titre in sera of vaccinated hens. After H5N1 infection at the age of 14 days, chickens with maternal antibody titres lived a few days longer than control chickens. However, only a low proportion of chickens with maternal immunity survived challenge with H5N1. In most progeny chickens with maternal immunity, high virus titres (>104 median embryo infective dose) were present in the trachea during the first 4 days after H5N1 infection. In the cloaca, only low virus titres were present in most chickens. In 14-day-old progeny chickens with maternal immunity, the induction of antibody titres by vaccination was severely inhibited, with only a few chickens showing responses similar to the control chickens. It is concluded that high maternal antibody titres are required for clinical protection and reduction of virus titres after infection of chickens, whereas low antibody titres already interfere with vaccine efficacy.

The Comparative Immunogenicity Of Three Lentogenic Brands Of Newcastle Disease Vaccines In Nigeria

The comparative immunogenicity of a new lentogenic viscerotropic Newcastle disease vaccine, NDvac-1 (VG/GA strain) and two other existing proprietary pneumotropic lentogenic Newcastle disease vaccines in Nigeria, NDvac-2 (R2B) and NDvac-3 (LaSota) were studied. Immunogenicity was assessed on the basis of antibody production and protectively ratio indices following experimental challenge. Results showed that the relatively high pre-vaccination maternal haemagglutination-inhibition antibody titres were counter-productive to effective vaccination at day old. The mean geometric titres were 2.4, 3.5, 2.1 and 4.4 for NDvac-1, double dose NDvac-1, NDvac-2 and NDvac-3 vaccinated groups respectively at day 20 post vaccination. The protection indices were 2.5, 2.5, 1.5, 3.0 and 1.0 for NDvac-1; double dose NDvac-1, NDvac-2, NDvac-3 and the unvaccinated control group respectively following experimental challenge. These results therefore presented superior immunogenicity shared by NDvac-3 and NDvac-1 while NDvac-2 was found to be the least immunogenic of the three vaccines. Keywords: Comparative immunogenicity, Newcastle disease vaccinesNigerian Veterinary Journal Vol. 28 (2) 2007 pp. 1-5

ASSESSMENT OF NEWCASTLE DISEASE VACCINATION OF HOUBARA BUSTARD BREEDERS (CHLAMYDOTIS UNDULATA UNDULATA)

The houbara bustard (Chlamydotis undulata undulata) is endangered in North Africa. Through a captive-breeding program established in Morocco by The Emirates Center for Wildlife Propagation, wild populations are being supplemented by the releasing of captive-reared birds. Newcastle disease, which is caused by Newcastle disease virus (NDV; Avian paramyxovirus type 1), can infect houbara bustards and is a significant threat through contact with backyard poultry and possibly wild birds. Three vaccination schedules for Newcastle disease were evaluated by serologic monitoring to assess the efficiency and safety of various types of vaccines (live vs. inactivated), vaccine strains (Hitchner B1 and Clone 30), and administration routes (intranasal vs. injection). We evaluated antibody titers in 211 adult houbara bustards for 10 mo. Antibody titers to NDV in both sera and egg yolks were monitored by hemagglutination inhibition test. The inactivated vaccine provided a high, homogeneous, and durable serologic response in breeders; titers were higher than log2 11 after 4 wk and remained higher than log2 7 after 10 mo. The response to the two live vaccines was similar, and antibody titers did not exceed log2 6 at sero-conversion. Maternally derived antibodies were efficiently transmitted in vitellus, further confirming that offspring of females hyperimmunized with the inactivated vaccine received high titers of maternal antibodies.

Maternal Exposure to Toxoplasmosis and Risk of Schizophrenia in Adult Offspring

The authors examined the relationship between maternal antibody to toxoplasmosis and the risk of schizophrenia and other schizophrenia spectrum disorders in offspring. Toxoplasmosis is known to adversely affect fetal brain development. In a nested case-control design of a large birth cohort born between 1959 and 1967, the authors conducted serological assays for Toxoplasma antibody on maternal serum specimens from pregnancies giving rise to 63 cases of schizophrenia and other schizophrenia spectrum disorders and 123 matched comparison subjects. Toxoplasma immunoglobulin (Ig)G antibody was quantified by using the Sabin-Feldman dye test. The Ig titers were classified into three groups: negative (<1:16) (reference), moderate (1:16-1:64), and high (> or =1:128). The adjusted odds ratio of schizophrenia/schizophrenia spectrum disorders for subjects with high maternal Toxoplasma IgG antibody titers was 2.61 (95% confidence interval=1.00-6.82). There was no association between moderate Toxoplasma Ig antibody titers and the risk of schizophrenia/spectrum disorders. These findings suggest that maternal exposure to toxoplasmosis may be a risk factor for schizophrenia. The findings may be explained by reactivated infection or an effect of the antibody on the developing fetus. Given that toxoplasmosis is a preventable infection, the findings, if replicated, may have implications for reducing the incidence of schizophrenia.

Development of maternal antibodies after oral vaccination of young female wild boar against classical swine fever

An experimental study was performed to investigate the development of maternal antibodies after oral immunisation of young female wild boar against classical swine fever (CSF) using C-strain vaccine. Our results demonstrated that maternal antibodies do not persist in the offspring for more than 3 months. Based on the neutralising serum antibody titres, we assume that piglets of wild sows vaccinated orally twice or immunised once a long time before conception have protective antibodies for approximately 2 months. Furthermore, it seems that the level and the duration of maternal antibodies in the offspring are depend on the age of the female animals at the moment of vaccination as demonstrated in our experiment. The recent vaccination procedure consists of three double vaccinations in spring, summer and autumn. Especially vaccinations in summer and autumn could be crucial for transfer of high maternal antibody titres to the offspring.

The effect of maternal antibodies on the detection of bovine virus diarrhoea virus in peripheral blood samples

Persistently infected animals (PI animals), that is those animals born after an intrauterine infection of the dam during the first 120 days of gestation, are the main source of bovine virus diarrhoea virus (BVD virus) in a cattle population. The success of any BVD virus eradication programme depends on the ability to detect all PI animals at a young age. The purpose of this study was to evaluate the use of the antigen ELISA test and the reverse transcriptase-polymerase chain reaction (RT-PCR) test for the diagnosis of PI animals in the presence of maternal antibodies, and to compare them with the classical virus isolation test. In this experiment, 25 calves born after an experimental infection with a mixture of BVD virus field strains were used. All calves were found to be positive for BVD virus using the virus isolation test, both before the ingestion of colostrum and again at 10 weeks of age. Both the virus isolation test and the antigen ELISA test were shown to be unreliable indicators for the diagnosis of persistent infections with BVD virus, when used in the presence of high levels of maternal antibodies. However, the RT-PCR test gave positive results even in the presence of high maternal antibody titres, indicating the suitability of the RT-PCR test for use in eradication programmes.

Early DNA vaccination of puppies against canine distemper in the presence of maternally derived immunity

Canine distemper (CD) is a disease in carnivores caused by CD virus (CDV), a member of the morbillivirus genus. It still is a threat to the carnivore and ferret population. The currently used modified attenuated live vaccines have several drawbacks of which lack of appropriate protection from severe infection is the most outstanding one. In addition, puppies up to the age of 6–8 weeks cannot be immunized efficiently due to the presence of maternal antibodies. In this study, a DNA prime modified live vaccine boost strategy was investigated in puppies in order to determine if vaccinated neonatal dogs induce a neutralizing immune response which is supposed to protect animals from a CDV challenge. Furthermore, a single DNA vaccination of puppies, 14 days after birth and in the presence of high titers of CDV neutralizing maternal antibodies, induced a clear and significant priming effect observed as early as 3 days after the subsequent booster with a conventional CDV vaccine. It was shown that the priming effect develops faster and to higher titers in puppies preimmunized with DNA 14 days after birth than in those vaccinated 28 days after birth. Our results demonstrate that despite the presence of maternal antibodies puppies can be vaccinated using the CDV DNA vaccine, and that this vaccination has a clear priming effect leading to a solid immune response after a booster with a conventional CDV vaccine.

A Field Study of Naturally Occurring Specific Antibodies against Clostridium perfringens Alpha Toxin in Norwegian Broiler Flocks

Necrotic enteritis (NE), a disease associated with high numbers of the intestinal bacterium Clostridium perfringens, is common in intensive broiler production. Antimicrobial feed additives may control the disease, but their use is now being questioned in many countries. A field study was undertaken at the end of 1997 to study the level of naturally occurring specific humoral immunity against phospholipase C (PLC; C perfringens alpha toxin) in Norwegian broiler flocks. Blood samples were collected at hatch from 61 study flocks, and the sampling was repeated for 56 of the same flocks at processing. The level of specific antibodies against PLC was analyzed in an enzyme-linked immunosorbent assay (ELISA) test. Data on production performance and weekly mortality were recorded. The relationship between the age of the hens and the level of specific maternal antibodies in the progenies was studied. The association between the level of the maternal antibodies and the production performance, including mortality, was analyzed. The level of specific antibodies against PLC in day-old broiler flocks was relatively high and varied considerably compared with the levels in the broilers at processing. The progenies from the oldest hens had significantly higher levels of specific antibodies than the chicks from younger hens. No outbreak of NE occurred during the study period, making it impossible to analyze the association between naturally occurring specific immunity against PLC and the occurrence of the disease. However, the results showed that the flocks with high titers of specific maternal antibodies against PLC had lower mortality during the production period than flocks with low titers.

Protective efficacy against respiratory syncytial virus following murine neonatal immunization with BBG2Na vaccine: influence of adjuvants and maternal antibodies.

Alum-adsorbed BBG2Na, a recombinant vaccine derived in part from the respiratory syncytial virus (RSV) subgroup A G protein, induced moderate antibody titers after 1 immunization in 1-week-old mice but conferred complete lung protection upon RSV challenge. The anti-BBG2Na IgG1-IgG2a neonatal isotype profile was suggestive of dominant Th2 responses compared with those in adults. Formulation of BBG2Na with a Th1-driving adjuvant efficiently shifted neonatal responses toward a more balanced and adultlike IgG1-IgG2a profile without compromising its protective efficacy. BBG2Na-induced protective immunity was maintained even after early life immunization in the presence of high titers of maternal antibodies. Under these conditions, the protective efficacy (86%-100%) reflected the high capacity of the nonglycosylated G2Na immunogen to escape inhibition by RSV-A-induced maternal antibodies. Thus, immunization with BBG2Na protected against viral challenge despite neonatal immunologic immaturity and the presence of maternal antibodies, two major obstacles to neonatal RSV vaccine development.