Effect Of Maternal Immunization Research Articles

Influenza subtype-specific maternal antibodies protect offspring against infection but inhibit vaccine-induced immunity and protection in mice

Following influenza A virus (IAV) infection or vaccination during pregnancy, maternal antibodies are transferred to offspring in utero and during lactation. The age and sex of offspring may differentially impact the transfer and effects of maternal immunity on offspring. To evaluate the effects of maternal IAV infection on immunity in offspring, we intranasally inoculated pregnant mice with sublethal doses of mouse-adapted (ma) H1N1, maH3N2, or media (mock) at embryonic day 10. In offspring of IAV-infected dams, maternal subtype-specific antibodies peaked at postnatal day (PND) 23, remained detectable through PND 50, and were undetectable by PND 105 in both sexes. When offspring were challenged with homologous IAV at PND 23, both male and female offspring had greater clearance of pulmonary virus and less morbidity and mortality than offspring from mock-inoculated dams. Inactivated influenza vaccination (IIV) against homologous IAV at PND 23 caused lower vaccine-induced antibody responses and protection following live virus challenge in offspring from IAV than mock-infected dams, with this effect being more pronounced among female than male offspring. At PND 105, there was no impact of maternal infection status, but vaccination induced greater antibody responses and protection against challenge in female than male offspring of both IAV-infected and mock-inoculated dams. To determine if maternal antibody or infection interfered with vaccine-induced immunity and protection in early life, offspring were vaccinated and challenged against a heterosubtypic IAV (i.e., different IAV group than dam) at PND 23 or 105. Heterosubtypic IAV maternal immunity did not affect antibody responses after IIV or protection after live IAV challenge of vaccinated offspring at either age. Subtype-specific maternal IAV antibodies, therefore, provide protection independent of offspring sex but interfere with vaccine-induced immunity and protection in offspring with more pronounced effects among females than males.

Adjuvants to increase immunogenicity of SARS-CoV-2 RBD and support maternal-fetal transference of antibodies in mice.

Adjuvants are important components of vaccines, increasing immunogenicity and modulating the immune response. SARS-CoV-2 vaccines are still being developed in order to improve worldwide access to immunization. Specific populations should be addressed in these investigations, such as pregnant women-to protect both mothers and neonates. In this study, female adult mice were immunized with Receptor-binding domain (RBD) from SARS-CoV-2 adjuvanted by a mixture of DDA and Saponin and put to mating to verify the maternal transference of IgG. For comparison, other group received RBD adjuvanted by OMVs from Neisseria meningitidis and Alum. The adjuvants enhanced IgG production and neutralization. DDA/Sap contributed to increase IgG1, IgG2a, IgG2b, and IgG3 isotypes. Total IgG avidity was considered high, as well as IgG1, IgG2a, and IgG2b avidity. IgG antibodies were effectively transferred to the offspring, predominantly IgG2a, IgG2b, and IgG3. The passive transferred immunoglobulin maintained the neutralizing ability, although it lost avidity. ELISA data was confirmed in Dot-ELISA and immunoblotting assays. DDA and Saponin seem a promising adjuvant mixture to enhance the humoral response of SARS-CoV-2 antigens. Further studies considering the effects of maternal immunization in the protection of offspring are needed, regardless the platform used in COVID-19 vaccines.

Effect of Maternal Immunization With 10-Valent Pneumococcus Conjugate Vaccine (PCV-10), 23-Valent Pneumococcus Polysaccharide Vaccine, or Placebo on the Immunogenicity of PCV-10 in Human Immunodeficiency Virus-Exposed Uninfected Infants: A Randomized Clinical Trial.

The effect of pneumococcal vaccination of mothers with human immunodeficiency virus (HIV) on infant responses to childhood vaccination has not been studied. We compared the immunogenicity of 10-valent pneumococcus conjugate vaccine (PCV-10) in HIV-exposed uninfected infants born to mothers who received PCV-10, 23-valent pneumococcus polysaccharide vaccine (PPV-23), or placebo during pregnancy. Antibody levels against 7 serotypes were measured at birth, before the first and second doses of PCV-10m and after completion of the 2-dose regimen in 347 infants, including 112 born to mothers who received PPV-23, 112 who received PCV-10, and 119 who received placebo during pregnancy. Seroprotection was defined by antibody levels ≥0.35 µg/mL. At birth and at 8 weeks of life, antibody levels were similar in infants born to PCV-10 or PPV-23 recipients and higher than in those born to placebo recipient. After the last dose of PCV-10, infants in the maternal PCV-10 group had significantly lower antibody levels against 5 serotypes than those in the maternal PPV-23 group and against 3 serotypes than those in the maternal placebo group, and they did not have higher antibody levels against any serotype. The seroprotection rate against 7 serotypes was 50% in infants in the maternal PCV-10 group, compared with 71% in both of the maternal PPV-23 and placebo groups (P < .001). Administration of PCV-10 during pregnancy was associated with decreased antibody responses to PCV-10 and seroprotection rates in infants. Considering that PCV-10 and PPV-23 had similar immunogenicity in pregnant women with HIV and that administration of PPV-23 did not affect the immunogenicity of PCV-10 in infants, PPV-23 in pregnancy may be preferred over PCV-10.

Protective Effect of Recombinant Proteins of Cronobacter Sakazakii During Pregnancy on the Offspring.

Cronobacter sakazakii is a food-borne pathogen carried in milk powder that can cause severe bacteremia, enterocolitis, and meningitis in newborns, which can lead to death of newborns. Preventing infection by this pathogen is significant to the health of newborns. Since infants and young children are the main target group of C. sakazakii, it is considered that maternal immunity can enhance the protection of newborns. Previous studies showed that two proteins of C. sakazakii (GroEL and OmpX) exhibited high expression levels and elicited strong immune reactions, suggesting their potential as vaccine candidates. In this study, GroEL and OmpX were recombinantly expressed in Escherichia coli and purified as immunogens to immunize pregnant rats. Three days after birth, the progeny were challenged with C. sakazakii to determine the protective effect of maternal immunity on the offspring. The results showed that immunization during pregnancy decreased bacterial load in the brain and blood, reduced brain and intestine damage, and significantly increased specific antibody titers in the offspring. Immunization with the recombinant proteins significantly increased cytokine levels in the serum of the progeny. The group whose mothers were immunized with OmpX produced more IL-4, while the group whose mothers were immunized with GroEL produced more IFN-γ, indicating that the immunogens enhanced the Th2 and Th1 responses, respectively. However, although the immune response was induced by both proteins, only the offspring of the pregnant rats immunized with OmpX or OmpX/GroEL mixture showed delayed death, possibly because immunization with OmpX led to a stronger humoral immune response in the offspring, suggesting that OmpX was a better vaccine candidate than GroEL. This study first reported that exposure to C. sakazakii proteins during pregnancy could improve the offspring's ability to resist infection caused by this pathogen.

Maternal immunity of tilapia broodstock vaccinated with polyvalent vaccine and resistance of their offspring againstStreptococcus agalactiae

This study aimed to examine the use of Streptococcus agalactiae polyvalent vaccine in tilapia broodstock and the effect of maternal immunity and resistance on their offspring against S. agalactiae strain. The broodstock was injected with polyvalent vaccine of S. agalactiae at a dose of 108 CFU per fish at 2nd gonadal maturity until spawning. Challenge test was carried out on the offspring at the 5, 10, 15 and 20 days after hatching using NK1, N17O, N14G, N3M, N4M strain respectively and combination of them. We observed immunological parameters in broodstock, eggs and larvae and relative per cent survival (RPS) of larvae after challenged with pathogenic S. agalactiae. The results showed that the leukocytes, phagocytic activity, respiratory burst, lysozyme activity and antibody levels of vaccinated broodstock had higher level compared with unvaccinated broodstock. The high level of the lysozyme activity, antibody levels and recombination activating gene 1 (RAG1) were also observed in eggs and larvae from vaccinated broodstock. Larvae produced from vaccinated broodstock when challenged with variety strain of pathogenic S. agalactiae had RPS value more than 50% until 20 days after hatching. In conclusion, polyvalent vaccine of S. agalactiae administrated in the broodstock could enhance immunity in the broodstock and protect their offspring from pathogenic S. agalactiae.

Effectiveness of maternal immunization with trivalent inactivated influenza vaccine in pregnant women and their infants.

In randomized trials, it has been found that maternal influenza vaccination reduces influenza infections in both women and their infants. However, these trials have been performed in low-resource settings, and evidence from high-resource settings is limited. Nested within a register-based cohort of all women giving birth in Denmark between 2010 and 2016 (n=357810 births), we conducted two case-control studies using a test-negative design of all pregnant women and their infants, respectively, tested for influenza virus with reverse transcriptase-polymerase chain reaction. Influenza virus-positive cases were matched (1:1) with influenza virus-negative controls for calendar time and (gestational or infant) age at testing. The effectiveness of maternal immunization with trivalent inactivated influenza vaccine was estimated from the odds ratios of vaccination among cases versus controls using logistic regression with adjustment for potential confounders. Among 313 pregnant women positive for influenza virus, 16 (5.1%) were vaccinated; by comparison, 34 (10.9%) pregnant women were vaccinated among 313 matched influenza virus-negative controls. The effectiveness of vaccination against laboratory-confirmed influenza infection in pregnant women was 63.9% [95% confidence interval (CI), 29.1 to 81.6]. Among 460 infants positive for influenza virus, 23 (5.0%) were offspring of women vaccinated during pregnancy; by comparison, 52 (11.3%) infants were the offspring of women vaccinated during pregnancy among 460 matched influenza virus-negative controls. The effectiveness of maternal vaccination against laboratory-confirmed influenza infection in infants younger than 6months of age was 56.8% (95% CI, 25.0 to 75.1). Seasonal trivalent inactivated influenza vaccination in pregnancy was associated with a statistically significant reduced risk of laboratory-confirmed influenza infections in pregnant women and their infants in a high-resource setting.

The effect of maternal immunity on the equine gammaherpesvirus type 2 and 5 viral load and antibody response.

Two types of gammaherpesviruses (γEHV) are known to infect horses, EHV-2 and EHV-5. Foals become infected early in life, probably via the upper respiratory tract, despite maternal antibodies. In this study, we analyzed samples from a herd of mares and their foals. The foals were followed from birth to 22 months of age and the dams during the first 6 months postpartum. Blood and nasal swab samples were taken regularly for evaluation of antibody responses, virus isolation and viral load by qPCR. EHV-2 was isolated on day 5, and EHV-5 on day 12, earlier than previously reported. γEHV specific antibodies were not detectable in serum of foals before colostrum intake but peaked a few days after colostrum. Overall, EHV-2 viral load peaked in nasal swab at three to four months of age, paralleled with decline in maternal antibodies, but EHV-5 viral load did not peak until month 12. Maternal antibodies had a notable effect on the viral load and induction of endogenous antibody production. Foals were grouped in two groups depending on the mare’s γEHV specific total IgG levels in serum at birth, group-high and group-low. Group-high had higher levels of maternal γEHV specific total IgG and IgG4/7 for the first 3 months, but when the endogenous production had superseded maternal antibodies, group-low was higher. The maternal antibodies had an effect on the γEHV viral load. Group-low peaked in EHV-2 viral load one month earlier than group-high. These effects were more evident for EHV-5, as there were seven months between the viral load peaks for the groups. The study provides information on how maternal antibody transfer affects γEHV shedding and antibody production in offspring. It also extends our knowledge on the occurrence of EHV-2 and EHV-5 infection in foals during the first two years of life.

Effectiveness of Maternal Immunization With Boostrix at Preventing Pertussis Among Infants &lt;2 Months Old in the United States

Effectiveness of Maternal Immunization With Boostrix at Preventing Pertussis Among Infants &lt;2 Months Old in the United States

Research progress of maternal immunization

Maternal immunization is an immune strategy that protects both mothers and early-life infants from disease by the vaccination of pregnant women. The effect of maternal immunization is influenced by the types of vaccines, the timing of vaccination, the subtypes of antibodies induced by vaccines, and the health status of mothers themselves. Inactivated influenza vaccination during pregnancy and DPT vaccination during the third trimester of pregnancy have been widely used in the world, while Hepatitis B vaccine, pneumococcal and meningococcal vaccines also show good efficacy and safety in pregnant women. This article reviews the research progress of Maternal Immunization in order to provide a reference for Maternal Immunization planning and policymaking in China.

Maternal Immunization.

Vaccines administered to women during pregnancy can provide protection against serious infectious diseases for the mother, for the newborn, or both. Maternal immunization boosts the concentration of maternal antibodies that can be transferred across the placenta to directly protect infants too young to be immunized. In addition, indirect protection through prevention of maternal infection and through breast milk antibodies can be achieved through maternal immunization. In general, inactivated vaccines are considered safe for pregnant women and their fetuses, whereas live vaccines are avoided owing to the theoretical potential risk to the fetus. However, the risks and benefits of vaccination must be carefully weighed and whenever possible, protection to the mother and her infant should be prioritized. Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines are routinely recommended for all pregnant women in the United States. Seasonal inactivated influenza vaccine is recommended for all pregnant women in any trimester of pregnancy, mainly to protect the mother, but there is growing evidence that infants benefit from passive antibody protection against influenza complications. The Tdap vaccine is recommended during the third trimester of each pregnancy to provide optimal protection to infants who are at particularly high risk of pertussis complications and mortality in the first 3 months of life. The effects of maternal immunization on the prevention of maternal and infant disease have been demonstrated in observational and prospective studies of influenza and pertussis disease in the United States and worldwide. Maternal immunization has the potential to improve the health of mothers and young infants and therefore, other diseases of relevance during this period are now targets of active research and vaccine development, including group B streptococcus and respiratory syncytial virus. Similarly, several vaccines can be administered during pregnancy in special circumstances, when maternal health, travel, or other special situations arise. This article reviews the current recommendations for vaccination of women during pregnancy.

Maternal immunization downregulates offspring TCD4 regulatory cells (Tregs) thymic maturation without implications for allergy inhibition.

The regulation of offspring allergy development mediated by maternal immunization was evidenced by several groups, and this mechanism seems to involve the induction of regulatory T cells (Tregs) on offspring. Here, we aimed to evaluate whether the effect of maternal immunization on offspring Tregs occurs as a result of peripheral or central modulation. Briefly, C57BL/6 female mice were immunized with OVA in Alum or Alum alone and boosted with OVA in saline or saline only after 10 and 20days. Non-immunized offspring serum, thymus and spleen were evaluated at 3 or 20days old, and some groups of pups were submitted to neonatal OVA-immunization protocol for the subsequent evaluation of antibody production and allergic response. Our experimental protocol could be validated because maternal OVA-immunization inhibited offspring allergic response as evidenced by the suppression of offspring IgE production and allergic lung inflammation. Interestingly, maternal immunization reduced the frequency of offspring thymic Tregs with an opposite effect on spleen Tregs. Furthermore, after neonatal immunization, the frequency of lung-infiltrated Tregs was also augmented on offspring from immunized mothers. In conclusion, maternal OVA-immunization can inhibit the thymic maturation of offspring Tregs without implications on peripheral Tregs induction and allergy inhibition.

Effect of maternal immunization against pertussis in Medellin and the metropolitan area, Colombia, 2016–2017

BackgroundIn 2013, pertussis immunization (Tdap) for pregnant women was implemented in Colombia to protect newborns in response to increased pertussis incidence. ObjectiveTo assess the effect of Tdap maternal immunization on the concentration of mother/umbilical cord antibodies and the occurrence of pertussis in infants during their first six months of life. MethodsA cohort study in eight randomly selected hospitals in Medellin and metropolitan area of Antioquia, Colombia was conducted in 2015–2016. IgG PT antibody levels in paired maternal and umbilical cord sera were measured from 805 mothers immunized recruited during labor and 200 mothers recruited during the prenatal care before immunization and followed until delivery. Antibodies were analyzed by commercial ELISA kits. 896 infants were followed to detect acute respiratory infections and paroxysms of coughing, inspiratory whoop, apnea, cyanosis or post-tussive vomiting. For laboratory confirmation, B. pertussis- specific real time PCR was performed. ResultsWe observed a high prevalence of titers >100 IU/mL (mother: 18.40% [95% CI 16–21%]; umbilical cord: 23.1% [95% CI 19.2–27.4%]), positive correlation of umbilical cord and maternal antibodies, higher antibody concentration in vaccinated than in non-vaccinated mothers and significant difference in antibody levels before and after vaccination (Wilcoxon test p = 0.000). The trans placental transport ratio was higher if the mother was vaccinated between 26 and 30 weeks of pregnancy and maximum eight weeks before delivery. Two cases of pertussis were confirmed in infants (incidence of 1.99 per 1000). ConclusionThe expected effect of Tdap maternal vaccination against pertussis was observed.

Maternal antibodies protect offspring from severe influenza infection and do not lead to detectable interference with subsequent offspring immunization

BackgroundVarious studies have shown that infants under the age of 6 months are especially vulnerable for complications due to influenza. Currently there are no vaccines licensed for use in this age group. Vaccination of pregnant women during the last trimester, recommended by the WHO as protective measure for this vulnerable female population, may provide protection of newborns at this early age. Although it has been observed that maternal vaccination can passively transfer protection, maternal antibodies could possibly also interfere with subsequent active vaccination of the offspring.MethodsUsing a mouse model, we evaluated in depth the ability of maternal influenza vaccination to protect offspring and the effect of maternal immunization on the subsequent influenza vaccination of the offspring. By varying the regimen of maternal immunization we explored the impact of different levels of maternal antibodies on the longevity of these antibodies in their progeny. We subsequently assessed to what extent maternal antibodies can mediate direct protection against influenza in their offspring, and whether these antibodies interfere with protection induced by active vaccination of the offspring.ResultsThe number of immunizations of pregnant mice correlates to the level and longevity of maternal antibodies in the offspring. When these antibodies are present at time of influenza challenge they protect offspring against lethal influenza challenge, even in the absence of detectable HAI titers. Moreover, no detectable interference of passively-transferred maternal antibodies on the subsequent vaccination of the offspring was observed.ConclusionIn the absence of a licensed influenza vaccine for young children, vaccination of pregnant women is a promising measure to provide protection of young infants against severe influenza infection.

Neonatal protection and preterm birth reduction following maternal group B streptococcus vaccination in a mouse model

Purpose: Evaluate effects of maternal immunization in a mouse model of Group B Streptococcus (GBS) vaginal colonization using clinical isolates.Materials and methods: Female pregnant mice were immunized with heat-killed GBS 21 days before pregnancy and were inoculated intravaginally with GBS cultures (5 × 107 CFU twice a day for three days) from the 16th day of pregnancy. Gestation period and mice survival were monitored. Maternal anti-GBS IgG levels have been determined by ELISA analysis in vaccinated, unvaccinated mothers and newborns.Results: Maternal immunization before pregnancy provided protection to newborns for three of the four GBS strains used. Evaluation of the immunogenicity showed that this vaccination induced higher levels of IgG in vaccinated compared to unvaccinated dams and the presence of antibodies in the offspring at embryonic and postnatal age, and a Th1 response and high levels of IgG2a subclass antibody and IFN-γ were detected. A significant reduction of preterm births was observed in vaccinated mothers (p< 0.05).Conclusions: Our finding suggest that vaccinated mothers could protect their progeny from GBS infection and preterm birth through passive immunization. The proposed mouse model may represent a noninvasive and effective tool to investigate pathogenetic mechanisms of GBS ascending infection and for vaccine protection studies.

Sustained Effectiveness of the Maternal Pertussis Immunization Program in England 3 Years Following Introduction.

The effectiveness of maternal immunization in preventing infant pertussis was first demonstrated in England, 1 year after the program using diphtheria–tetanus–5-component acellular pertussis–inactivated polio vaccine (dT5aP-IPV) was introduced in 2012. Vaccine effectiveness against laboratory-confirmed pertussis has been sustained >90% in the 3 years following its introduction, despite changing to another acellular vaccine with different antigen composition. Consistent with this, disease incidence in infants <3 months of age has remained low despite high activity persisting in those aged 1 year and older. Vaccine effectiveness against infant deaths was estimated at 95% (95% confidence interval, 79%–100%). Additional protection from maternal immunization is retained in infants who received their first dose of the primary series. There is no longer evidence of additional protection from maternal vaccination after the third infant dose. Although numbers are small and ongoing assessment is required, there is no evidence of increased risk of disease after primary immunization in infants whose mothers received maternal vaccination.

Activation of maternal toll-like receptor-2 causes social deficits and memory impairment in female offspring.

To study the relevance of the activation of toll-like receptor-2 and abnormal behavioral properties, we introduced prenatal zymosan, a toll-like receptor-2 ligand, to investigate the effect of maternal immunity on offspring behavior. Only female offspring showed impaired social and cognitive function, suggesting that zymosan may influence females' behavior.

The effect of maternal immunization on female oxidative status, yolk antioxidants and offspring survival in a songbird

Immune defense involves inflammatory reactions in which immune cells produce reactive oxygen species (ROS) to fight pathogens. ROS may however cause damage to the host if they are not balanced by antioxidant defenses. Therefore, one should expect individuals undergoing an immune reaction to use antioxidants to prevent oxidative stress. Antioxidants are vital compounds that provide important protection against oxidative damage of embryos and newly hatched chicks. Thus, during egg laying a female that contracted an infection may face a trade-off between the allocation of antioxidants into self-maintenance and into her offspring via the eggs. In our study we investigated whether immunized females face this trade-off and consequently modify the antioxidant allocation into the eggs and whether this allocation affects offspring performance. We injected female zebra finches (Taeniopygia guttata) with lipopolysaccharide prior to egg laying while some females were left unimmunized. We removed the second egg of each clutch, while we allowed the other eggs to hatch. We assessed oxidative stress in females 24h after immunization, yolk antioxidant capacity of the second egg of the clutch and survival success of the offspring until adulthood. Compared to controls, immunized females had higher oxidative damage, but similar plasma non-enzymatic antioxidant levels. The treatment did not affect yolk antioxidants, clutch size, laying date and offspring survival. However, we found a positive correlation between yolk antioxidant capacity and offspring survival, irrespective of the treatment. Our study suggests that our immune challenge may not have changed female strategy of antioxidant allocation between self-maintenance and offspring survival.

The effects of maternal immunity and age structure on population immunity to measles.

Measles was successfully eradicated in the Pan-American Health Region in 2002. However, maintenance of elimination in parts of Africa, Europe, the USA, and other regions is proving difficult, despite apparently high vaccine coverage. This may be due to the different age structure in developed and developing populations, as well as to differences in the duration of maternal immunity. We explore the interaction between maternal immunity and age structure and quantify the resulting immunity gap between vaccine coverage and population immunity; we use this immunity gap as a novel metric of vaccine program success as it highlights the difference between actual and estimated immunity. We find that, for some combinations of maternal immunity and age structure, the accepted herd immunity threshold is not maintainable with a single-dose vaccine strategy for any combination of target age and coverage. In all cases, the herd immunity threshold is more difficult to maintain in a population with developing age structure. True population immunity is always improved if the target age at vaccination is chosen for the specific combination of maternal immunity and age structure.Electronic supplementary materialThe online version of this article (doi:10.1007/s12080-014-0250-8) contains supplementary material, which is available to authorized users.

Colostral antibody induced interference of inactivated bluetongue serotype-8 vaccines in calves

Since its introduction into northern Europe in 2006, bluetongue has become a major threat to animal health. While the efficacy of commercial vaccines has been clearly demonstrated in livestock, little is known regarding the effect of maternal immunity on vaccinal efficacy. Here, we have investigated the duration and amplitude of colostral antibody-induced immunity in calves born to dams vaccinated against bluetongue virus serotype 8 (BTV-8) and the extent of colostral antibody-induced interference of vaccination in these calves. Twenty-two calf-cow pairs were included in this survey. The median age at which calves became seronegative for BTV was 84 and 112 days as assayed by seroneutralisation test (SNT) and VP7 BTV competitive ELISA (cELISA), respectively. At the mean age of 118 days, 13/22 calves were immunized with inactivated BTV-8 vaccine. In most calves vaccination elicited a weak immune response, with seroconversion in only 3/13 calves. The amplitude of the humoral response to vaccination was inversely proportional to the maternal antibody level prior to vaccination. Thus, the lack of response was attributed to the persistence of virus-specific colostral antibodies that interfered with the induction of the immune response. These data suggest that the recommended age for vaccination of calves born to vaccinated dams needs to be adjusted in order to optimize vaccinal efficacy.

Modeling Variability in Immunocompetence and Immunoresponsiveness

The purposes of this paper were to 1) develop a stochastic model that would reflect observed variation between animals and across ages in immunocompetence and responsiveness; and 2) illustrate consequences of this variability for the statistical power of genotype comparisons and selection. A stochastic model of immunocompetence development and responsiveness kinetics was developed. This model enabled variability in immunological variables to be taken into account in the evaluation of challenge and measurement strategies for selection. The characteristics of the variation in model output reflect those observed in the literature, to the extent that variation in the literature shows a consistent pattern; knowledge of true variation and patterns of variation in immunological variables is limited. The model created correlations between immunocompetence and immunoresponsiveness components, as well as correlations within each component across time. These correlations were generally in agreement with literature estimates, where available. The model enabled predictions of the effectiveness of selection for improved health through immunocompetence or immunoresponsiveness. It was predicted that effective selection for increased general immunocompetence to improve health should be done only when baseline immunity has matured. Further, the model implied that selection is unlikely to be successful if it is based only on a single measurement. Problems with low statistical power to detect differences between genotypes can be reduced by increasing challenge age in the experimental design, and one should ensure that the effects of maternal immunity are minimal when the challenge is done. The ability to detect differences between different groups of animals differs substantially with measurement timing because of low repeatabilities of immunocompetence and responsiveness across time. In general, the probability of detecting differences becomes higher when the challenge age is increased. Consequently, both the age at selection and the age at which information is gathered for selection must be considered carefully when designing genetic evaluations.