Antibody responses to parenteral and oral vaccines are impaired by conventional and low protein formulas as compared to breast-feeding

The vaccine response to poliovirus, diphtheria and tetanus toxoids in relation to protein intake was studied in infants, either breast-fed or given low (1.1 g/100 ml) or conventional (1.5 g/100 ml) protein formula. Serum, saliva and faeces antibodies were measured by the enzyme-linked immunosorbent assay. Neutralizing poliovirus antibodies were determined. The serum, saliva and faeces antibody responses in the two formula-fed groups of infants did not differ significantly, but for the low protein formula group which had significantly higher serum neutralizing titres to poliovirus after the second vaccine dose than the conventional formula group. However, the breast-fed group had significantly higher antibody levels than the two formula-fed groups together: serum IgG to diphtheria toxoid (p less than 0.01) and serum neutralization of poliovirus (p less than 0.001) at 21-40 months of age, saliva secretory IgA to tetanus (p less than 0.01), diphtheria toxoid (p less than 0.01) and poliovirus (p less than 0.05), as well as faecal IgM to tetanus toxoid (p less than 0.05) and poliovirus (p less than 0.01 and p less than 0.05) at 3 and 4 months of age. Breast-fed infants thus showed better serum and secretory responses to peroral and parenteral vaccines than the formula-fed, whether with a conventional or low protein content.     

Immune status of infants fed soy-based formulas with or without added nucleotides for 1 year: part 1: vaccine responses, and morbidity

BACKGROUND: Immunologic development of soy-fed infants has not been extensively studied. Early studies of soy flour-based formulas showed decreased immunoglobulin production when soy protein intake was limited. However, there were no significant differences in rotavirus vaccine responses between breast-fed and soy protein isolate-based formula-fed infants. Nucleotides added to milk-based formula benefit infant immune status, but reports of the immunologic effects of adding nucleotides to soy-based formula are not available. This study evaluated immune status and morbidity of infants fed soy protein isolate formulas with and without added nucleotides for 1 year. METHODS: Newborn, term infants enrolled in a masked 12-month feeding trial were assigned randomly to groups fed soy formula with or without added nucleotides (n = 94, n = 92). A nonrandomized human milk/formula cohort (n = 81) was concurrently enrolled. Recommended immunizations were administered at 2, 4, and 6 months. Immune status was determined from antibody responses to Haemophilus influenzae type b, tetanus, diphtheria, and poliovirus vaccines at 6, 7, and 12 months. Parents and physicians reported morbidity data. RESULTS: All vaccine responses were within normal ranges. No response differences were observed between infants fed soy formula and those fed nucleotide-supplemented soy. However, antibody to H. influenzae type b at 7 and 12 months was higher in infants fed nucleotide-supplemented soy than in infants fed human milk/formula ( P = 0.007, P = 0.008, respectively). Human milk/formula-fed infants had higher poliovirus neutralizing antibody at 12 months than did soy-fed infants ( P = 0.016). Morbidity analyses showed that only physician-reported diarrhea was different among groups (groups fed human milk/formula had less diarrhea than did soy groups, P = 0.011). CONCLUSIONS: Term infants fed soy protein isolate-based formulas have normal immune development as measured by antibody responses to childhood immunizations.     

Acute C-Peptide, Insulin and Branched Chain Amino Acid Response to Feeding in Formula and Breast Fed Infants

ABSTRACT. The response of C-peptide in serum and urine and of glucose and branched chain amino acids in blood to formula and breast feeding was assessed in six breast-fed and six formula-fed infants 3–6 months of age. We analysed serum C-peptide, branched chain amino acids (BCAA) in blood, and blood glucose in the fasting state at 90' and 180' after regular meal. The excretion of urinary C-peptide and creatinine was also determined. The formula-fed infants received formula in current use, containing 15–16 g protein/l and with casein/whey ratio of 40/60. In the fasting state, no significant inter-group difference was found in the level of serum C-peptide or the valine/glycine ratio. Postprandially, the formula-fed infants had significantly higher serum C-peptide values and valine/glycine ratio than the breast-fed infants, p ≤0.05. No significant inter-group difference was found for blood glucose. The urinary C-pep-tide/creatinine ratio was significantly lower in the breast-fed group, p =0.02, and significantly correlated both to the valine/glycine ratio at 90', r_s =0.75, p =0.02 and to the serum C-peptide value at 90', r_s =0.66, p =0.03. These results confirm that in formula-fed infants the insulin response to meal is enhanced compared to that in breast-fed infants. The finding of similar blood glucose values in the two groups may also indicate an insulin resistance in the formula-fed infants following meal.     

Absence of a significant interaction between a Haemophilus influenzae conjugate vaccine combined with a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine in the same syringe and inactivated polio vaccine

BACKGROUND: We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after three doses of a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine (DTaP) combined with a PRP-tetanus conjugate (PRP-T) in infants randomized to receive oral polio vaccine (OPV) or inactivated polio vaccine (IPV). The polio vaccine was given separately at the same visit. METHODS: Three hundred fifty-six infants from pediatric practices in suburban Chicago and New Orleans were randomized into two groups. Group A received OPV at 2 and 4 months of age; Group B received IPV at 2 and 4 months of age. Both groups received DTaP/PRP-T at 2, 4 and 6 months of age and hepatitis B vaccine at 2 and 4 months of age. A serum sample was obtained before immunization (age 2 months) and 1 month after 3 doses of DTaP/PRP-T (age 7 months). Sera were assayed for antibody responses to all relevant vaccine antigens. RESULTS: No significant vaccine antigen interference was found when polio immunization was provided by IPV or OPV for anti-PRP, diphtheria, tetanus or pertussis antibodies. OPV recipients had a significantly higher mean antibody response to serotype 1 (P = 0.03) and 2 (P = 0.0001) poliovirus. CONCLUSION: Whether polio immunization was accomplished with IPV or OPV did not significantly influence the antibody responses in sera obtained at 7 months of age for anti-PRP, anti-diphtheria and anti-tetanus toxoid antibodies and antibodies to pertussis antigens, when DTaP/PRP-T was given in the primary series.     

Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines.

Because of apparent differences in the incidence and epidemiology of pertussis in the United States and Canada, we measured the antibody response to four Bordetella pertussis antigens and to a whole-bacteria preparation in children immunized with American and Canadian whole-cell pertussis vaccines. All infants received combined pertussis, tetanus, and diphtheria vaccines from one of two American manufacturers or a single Canadian manufacturer. The Canadian children received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as a separate injection, or a product that combined inactivated poliomyelitis vaccine with diphtheria, tetanus, and pertussis components. The Canadian trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus vaccine induced lower anti-pertussis toxin antibody titers than did the American vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer-membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian children immunized with inactivated poliomyelitis vaccine either as a separate injection or as a combined diphtheria, tetanus, and pertussis vaccine had consistently lower pertussis antibody titers than did those who received oral poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of antibody responses to B. pertussis antigens after immunization with various whole-cell pertussis vaccines, and that these responses may be influenced by concurrent administration of other vaccines.     

A comparison of secretory antibodies in breast-fed and formula-fed infants over the first six months of life

In the present study salivary IgA, anti-Escherichia coli, anti-beta-lactoglobulin and anti-poliovirus type 1 IgA and IgM in serum and saliva were evaluated longitudinally in 13 breast-fed and 14 formula-fed infants over the first six months of life. Salivary IgA was quantified by electroimmunodiffusion; specific IgA and IgM antibodies were determined in serum and saliva by ELISA. Salivary IgA was significantly lower at age one month in breast-fed compared with formula-fed infants but in breast-fed infants salivary IgA increased with age and was significantly higher at six months than at one month. In both groups of infants, at the age of six months, salivary IgA levels were significantly lower than in adult controls. No significant differences in secretory anti-E. coli were observed between the two groups of infants. Salivary anti-poliovirus IgA and IgM antibodies increased transiently only to disappear in most babies at age six months, while anti-beta lactoglobulin IgA and IgM, present in saliva at all ages, showed a wide scatter. No important differences in specific serum IgA or IgM antibodies were observed either between the groups or at different times within the groups.     

DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation

Aims: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. Methods: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. Results: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 µg/ml with 80% ⩾0.15 µg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% ⩾8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with ⩾80% achieving protective rises in IgG against the five pertussis antigens. Conclusion: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.     

DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation.

AIMS: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. METHODS: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. RESULTS: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 microg/ml with 80% > or =0.15 microg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% > or =8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with > or =80% achieving protective rises in IgG against the five pertussis antigens. CONCLUSION: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.     

Comparison of Serum and Salivary Antibodies in Children Vaccinated with Oral Live or Parenteral Inactivated Poliovirus Vaccines of Different Antigen Concentrations

ABSTRACT. A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgC and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age ( p > 0.05). The serum IgC responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups ( p <0.01). For type 3, these titres were highest but not significantly, in the IPV4 group ( p > 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV ( p <0.05).     

Diphtheria, tetanus and pertussis antibodies in 10-year-old children before and after a booster dose of three toxoids: implications for the timing of a booster dose

In an open study, 502 10-year-old children, who had received primary vaccination against diphtheria and tetanus in infancy and had varying histories of pertussis disease and vaccination, were vaccinated with diphtheria-tetanus vaccine (DT) alone or with the addition of 20 µg or 40 g of pertussis toxoid. Diphtheria toxin neutralising antibodies, pertussis toxin IgG and tetanus toxoid IgG antibodies were measured before and 1 month after the booster. All toxoids were highly immunogenic. In pertussis toxoid recipients, median levels of pertussis toxin IgG increased to 16.5 U/ml (DTaP20) and to 36 U/ml (DTaP40) in children with non-detectable (<1 U/ml) antibodies before vaccination and to >400 U/ml in children (both DTaP20 and DTaP40) with detectable antibodies before vaccination. A total of 60 children (12%) with non-detectable (<0.01 IU/ml) diphtheria antibodies and 36 children (7%) with non-detectable (<0.01 IU/ml) tetanus antibodies before the booster had lower median antibody concentrations post-vaccination than children with detectable antibodies before the booster (diphtheria: 5.12 vs. 20.48 IU/ml; tetanus: 4.0 vs. 10.0 IU/ml). There were no differences in diphtheria and tetanus antibodies after vaccination between children who did and did not receive pertussis toxoid. Conclusion:10-year-old children with non-detectable diphtheria and tetanus antibodies before the booster had lower post-vaccination antibodies than those with detectable antibodies before the booster indicating a poor immunological memory. Addition of pertussis toxoid to diphtheria-tetanus vaccine did not affect the antibody responses to diphtheria and tetanus toxoids when the three toxoids were combined as a booster. Even though immunity to diphtheria and tetanus was only estimated by surrogate markers (serum antitoxin antibodies) the results indicate that a lower age for the booster dose of diphtheria-tetanus vaccine or diphtheria-tetanus acellular pertussis vaccine should be considered.     

Immunogenicity of Haemophilus influenzae type b conjugate vaccines in infant rhesus monkeys

Two Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines were evaluated for immunogenicity in eliciting anti-polyribosyl ribitol phosphate (PRP) antibodies in infant rhesus monkeys. Animals received intramuscular injections of either Hib polysaccharide (PRP)-meningococcal outer membrane protein complex or Hib oligosaccharide-CRM197 (HbOC) conjugate vaccines on d 0, 28, and 56. Because HbOC contains the CRM197 mutant diphtheria toxin from Corynebacterium diphtheriae as its protein carrier, the effect of simultaneous injection of diphtheria toxoid on the immunogenicity of HbOC also was evaluated by dividing monkeys vaccinated with HbOC into three groups: HbOC/saline, HbOC/diphtheria and tetanus toxoids, and HbOC/tetanus toxoid (coadministration of HbOC and other vaccine or placebo injected into the flank muscle of different legs). Infant monkeys vaccinated with the PRP-outer membrane protein complex conjugate responded with anti-PRP antibody after the first dose and showed booster responses after the second and third injections. In contrast, infant monkeys vaccinated with HbOC did not respond after three doses of HbOC/saline or HbOC/tetanus toxoid. However, two of three monkeys given concurrent injections of HbOC and diphtheria and tetanus toxoids did respond. The nonresponder monkey to three doses of HbOC and diphtheria and tetanus toxoids did respond to a subsequent injection with PRP-outer membrane protein complex. Thus, concomitant administration of diphtheria toxoid, a common vaccine for human infants, is necessary to elicit an anti-PRP antibody response to HbOC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trace elements (copper, zinc, manganese, and selenium) in plasma and erythrocytes in relation to dietary intake during infancy

All determinations of copper, zinc, manganese, and selenium were performed with a flameless atomic absorption spectrophotometer. Seventy-three full-term infants aged 1 to 52 weeks were divided into three age groups. Each age group contained two subgroups, breast-fed and formula-fed. No statistically significant differences between formula-fed and breast-fed subgroups were found in regard to the levels of copper and zinc in plasma and erythrocytes. At 1 to 5 weeks of age, the manganese concentration of erythrocytes was higher in formula-fed than in breast-fed infants (p less than 0.001). This might be due to the high dietary intake of this element in the formula-fed subgroup. On the other hand, plasma selenium concentrations were significantly higher in breast-fed than in formula-fed infants of all ages (p less than 0.01 at 1 to 5 weeks and p less than 0.05 at 6 to 52 weeks). This suggests that selenium compounds are biologically more available for infant nutrition in breast milk than in formula.     

Comparison of serum and salivary antibodies in children vaccinated with oral live or parenteral inactivated poliovirus vaccines of different antigen concentrations.

A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgG and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age (p greater than 0.05). The serum IgG responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups (p less than 0.01). For type 3, these titres were highest but not significantly, in the IPV4 group (p greater than 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV (p less than 0.05).     

Effect of dietary ribonucleotides on infant immune status. Part 1: Humoral responses

The objective of this study was to further explore previously identified effects of supplemental ribonucleotides on infant immune status as measured by antibody responses to routine infant immunizations. Infants were randomized to a milk-based formula with (FN, n = 138) or without (F, n = 147) 72 mg ribonucleotides/L. A cohort of human milk-fed (HMF, n = 192) infants was also followed. Subjects were given Haemophilus influenzae type b (Hib), diphtheria tetanus acellular pertussis, and oral poliovirus vaccinations at 2, 4, and 6 mo of age, and specific antibody responses were assessed at 2, 6, 7, and 12 mo. Growth and safety data were also monitored. Using a two-group repeated measures analysis (RMA), FN-fed infants had significantly higher poliovirus type 1 neutralizing antibody (PV-VN1) responses than F-fed infants (p = 0.045). Using three-group RMA, PV-VN1 responses in HMF infants were not different from FN-fed infants, while HMF-fed infant PV-VN1 responses were significantly higher than F-fed infants at 6 (p = 0.0004) and 12 mo (p = 0.0001). FN-fed infants had responses to Hib Farr, diphtheria, tetanus toxoid, oral poliovirus-specific IgA, and PV-VN3 not significantly different from those of F and HMF infants. Growth, gastrointestinal tolerance, and adverse events were equivalent among the three groups. The FN-associated increase in PV-VN1 response and nonstatistically significant trends toward increased Hib and diphtheria antibody responses were consistent with observations from earlier studies, indicating immune benefits of nucleotide supplementation of infant formula.     

Antibody response to an eleven valent diphtheria- and tetanus-conjugated pneumococcal conjugate vaccine in Filipino infants

BACKGROUND: Pneumococcal conjugate vaccines are intended to provide effective protection against pneumococcal infections, but very little information on antibody responses in infants living in countries with high pneumococcal disease burden exists. METHODS: In this study 50 healthy Filipino infants were enrolled at a village health center in Cabuyao to receive 11-valent diphtheria- and tetanus-conjugated pneumococcal vaccine at 6, 10 and 14 weeks of age (primary series) simultaneously with diphtheria-tetanus-whole cell pertussis/polyribosylribitol phosphate conjugated to tetanus toxoid, hepatitis B virus and oral poliovirus vaccines and at 9 months of age (booster dose) simultaneously with measles vaccine. The alum-adjuvanted study vaccine contained pneumococcal polysaccharide of serotypes 1, 4, 5, 7F, 9V, 19F and 23F conjugated to tetanus protein and pneumococcal polysaccharide of serotypes 3, 6B, 14 and 18C conjugated to diphtheria toxoid. Serum samples for enzyme immunoassay analyses were collected at 6, 10 and 14 weeks and 9 and 10 months of age. RESULTS: Very high geometric mean antibody concentrations (GMCs) against most pneumococcal serotypes were observed after the first three doses of vaccine (range, serotype 23F, 3.89 microg/ml to serotype 4, 23.41 microg/ml) with the exception of serotype 6B and 14, with GMCs of 1.12 and 2.18 microg/ml, respectively. The fourth dose increased the GMCs against most serotypes (range, serotype 14, 1.65 to serotype 19F, 33.43 microg/ml). The maternally derived antibodies did not decrease the response to the vaccine. CONCLUSIONS: This first pneumococcal conjugate vaccine study in Asia confirms that the 11-valent diphtheria- and tetanus-conjugated pneumococcal vaccine is highly immunogenic in Filipino infants. The GMCs against most pneumococcal serotypes were substantially higher than described with the same or other pneumococcal conjugate vaccines in other populations.     

Simultaneous administration of Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine with routine diphtheria-tetanus-pertussis and inactivated poliovirus vaccinations of childhood

A Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) is capable of protecting infants against invasive H. influenzae diseases. Therefore it is very likely that it will be incorporated in routine vaccination schedules during the next few years. In order to test the suitability of simultaneous administration of PRP-D and other vaccines we administered it to 25 infants mixed with diphtheria-tetanus-pertussis vaccine at 3, 4 and 6 months and simultaneously, but in a separate syringe, with inactivated polio vaccine at 12 months. A comparison group of equal size received only diphtheria-tetanus-pertussis and inactivated poliovirus vaccines. The concentration of postvaccination antibodies to diphtheria toxoid was 0.411 IU/ml in the group that received PRP-D vs. 0.352 IU/ml in the comparison group, to tetanus toxoid 3.666 vs. 3.668 IU/ml and the neutralization titer to poliovirus type 1 was 370 vs. 320 units in the comparison group, to type 2 titer values were 230 vs. 270 units and to type 3, respectively, 210 vs. 290 units. Thus the seroresponse to antigens in routine vaccines was not affected by the presence of PRP-D in the vaccination schedule, and PRP-D can safely and effectively be included in the vaccination schedule of infancy.     

Whey predominant,whey modified infant formula with protein/energy ratio of 1.8 g/100 kcal: adequate and safe for term infants from birth to four months

BACKGROUND: Protein quality of breast milk is superior to that of formula proteins. To ensure that the protein intake is sufficient, starter formulas with conventional protein composition provide a protein/energy ratio of 2.2-2.5 g per 100 kcal to infants, which is much higher than that supplied with breast milk. Several studies have shown that formula-fed infants have higher plasma or serum urea concentrations than breast-fed infants do. We tested if feeding formulas with improved protein quality and a protein content corresponding to the minimum level that is consistent with international recommendations (1.8 g/100 kcal) allows patients to achieve normal growth and plasma urea concentrations. METHODS: Healthy term infants were enrolled into the study and were either breast-fed or randomly assigned to three formula-fed groups. Formula-fed infants received either a standard formula with a protein/energy ratio of 2.2 g/100 kcal, whereas the two other groups received formulas with a protein/energy ratio of 1.8g/100 kcal differing mainly by their source of protein. Subjects received breast milk or these formulas ad libitum as the sole source of energy from birth to four months of age in a controlled blind design (except for the breast-fed group). Anthropometric measurements (body weight and length) were obtained at birth, at 30, 60, 90, and 120 days. Energy and protein intakes were calculated from three-day dietary records. Blood was collected for biochemical measurements at 30, 60, and 120 days. RESULTS: No differences were found between the four feeding groups for weight- and length-gains or for body mass indices (BMI). No differences in energy intakes between the formula-fed groups could be found, whereas protein intakes were less in infants fed the 1.8 g/100 kcal formulas. Plasma urea levels of the infants fed the 1.8 g/100 kcal formulas were closer to those found in the breast-fed infants. CONCLUSION: Improvement of the amino acid profile permits a whey predominant starter formula with 1.8 g protein per 100 kcal to meet the needs of normal term infants during the first four months of life.     

Reduced immunogenicity of diphtheria and tetanus toxoids when combined with pertussis toxoid

The effect of pertussis toxoid on the immunogenicity of diphtheria and tetanus toxoids (DT) was studied during a double blind efficacy trial of an acellular pertussis vaccine. Infants received DT with or without pertussis toxoid at 3, 5 and 12 months of age. Geometric mean concentrations were higher in the DT than in the DT-pertussis toxoid group 1 month (diphtheria toxoid 4.76 versus 3.58 IU/mL, P = 0.009; tetanus toxoid 4.42 versus 2.66 IU/mL, P < 0.0001) and 2 years after the third injection (diphtheria toxoid 0.15 versus 0.10 IU/mL, P < 0.0001; tetanus toxoid 0.38 versus 0.18 IU/mL, P < 0.0001). Pertussis toxoid causes a small but significant reduction of the immunogenicity of diphtheria toxoid and tetanus toxoid.     

Response to RIT 4237 Oral Rotavirus Vaccine in Human Milk, Adapted- and Soy-Formula Fed Infants

ABSTRACT. During the first month of life 28 full-term newborns were breast-fed (18 males and 11 females). Thereafter 8 infants continued breast-feeding while the remainder were randomly fed on either an adapted milk formula ( n =13) or a soy-formula ( n =7). At five months, after an oral dose of RIT 4237 rotavirus vaccine of bovine origin was given, growth and IgM/IgG type antibodies against rotavirus were measured. Weight gain was similar in all infants. There were 2 IgM and 1 IgG responders out of 7 soy fed infants, compared with 4 out of 8 human milk fed (both IgM and IgG) and 7 out of 13 IgM and 6/12 IgG formula fed infants responding to vaccination. This observation confirms previous results obtained with polio, diphtheria tetanus and pertussis vaccines indicating that soy-protein formulas may interfere with immunization processes.     

Titres of specific antibodies to poliovirus type 3 and tetanus toxoid in saliva and serum of children with recurrent upper respiratory tract infections

A study of antibody levels (in saliva and blood) against common vaccine antigens was performed in a population of 32 children suffering from recurrent upper respiratory tract infections (URTI). None of the patients had primary or secondary immunodeficiency syndromes or other known predisposing factors for respiratory diseases. Titres of the isotype-specific antibodies immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) against two vaccine antigens – poliovirus type 3 (P3) and tetanus toxoid (TT), a viral antigen and a bacterial antigen, respectively – were measured in unstimulated saliva and serum, both in patients and in 24 healthy children (controls), by using a standard enzyme-linked immunosorbent assay (ELISA). In addition, levels of total IgA and avidity of IgA antibodies to both P3 and TT in saliva were evaluated. No difference was found between patients and controls as to levels of total IgA, or specific IgA and IgM antibodies against both P3 and TT in saliva. Furthermore, the avidity of salivary IgA antibodies against the two antigens did not differ between the two populations. However, the average concentrations of saliva-specific IgG antibodies to both the viral and the bacterial antigen were significantly lower (p < 0.01 for P3 and p < 0.05 for TT, respectively) in saliva of children with recurrent URTI, whereas no difference was found in serum for any immunoglobulin isotype determined compared with healthy individuals. The results of the present study provide suggestive evidence for the existence of subtle IgG-restricted defects in antibody responses at the mucosal level, but not at the serum level, in some children with undue susceptibility to URTI.