Oral polio vaccination of children in the tropics. II. Antibody response in relation to vaccine virus infection.

Poliovirus antibody response rates following the administration of trivalent oral polio vaccine (OPV) have been poor in several developing countries. In an attempt to determine if poor seroresponse is due to poor rates of vaccine virus "take" or due to poor serum antibody response to intestinal virus infection, both vaccine virus take and serum antibody response were determined in a group of children given two doses of OPV. In the large majority of seronegative children there was good correlation between the absence or presence of vaccine virus excretion and negative or positive seroconversion, thus showing that the poor seroconversion rates were mainly due to poor rates of vaccine virus take. However, as in several studies from developed countries showing good seroconversion rates, a few instances of antibody response in the absence of detectable virus excretion and fewer instances of virus excretion without detectable antibody response were also found.     

Oral polio vaccine response in the MAL-ED birth cohort study: Considerations for polio eradication strategies

Background

Immunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3.

Oral polio vaccine response in breast fed infants with malnutrition and diarrhea

Oral vaccines for polio (OPV) and rotavirus are less effective in children in the developing world. The reasons for this are not well understood. We tested for risk factors for poor response to OPV in infants from an urban slum of Dhaka, Bangladesh. Diminished serum neutralizing response to OPV, but not failure of intramuscularly administered vaccines, was associated with malnutrition, diarrhea, and shorter breastfeeding duration. Children with malnutrition (WAZ <−2) had significantly lower OPV 3 titers (p = 0.029). Children who had 2 or more diarrhea episodes during the 1st months of life were more than twice as likely to experience OPV failure as those who had 1 diarrhea episode or no diarrhea (p = 0.0245). In contrast, each additional month in exclusive breastfeeding was associated with an increase in OPV 3 titer by 0.41 (p = 0.0072) and 0.16 (p = 0.0065) at the 25th and 50th percentiles of OPV 3 titers respectively. These data are consistent with a defect in induction of immunity in the gut for OPV but not parenteral vaccines, a defect that may be amenable to intervention in part via promotion of exclusive breastfeeding.     

Oral polio vaccination and low case fatality at the paediatric ward in Bissau, Guinea-Bissau

Oral polio vaccine (OPV) and diphtheria-tetanus-pertussis (DTP) vaccines are given simultaneously in routine immunisation programmes in developing countries. It is therefore difficult to determine the separate effects of these vaccines on survival. We used the shortage of DTP vaccine in Bissau to examine the impact of OPV on the case fatality at the paediatric ward in Bissau. For 719 children less than 5 years of age whose vaccination card had been seen at admission and who had not yet received measles vaccine, having received OPV only was associated with a case fatality of 6% compared with 15% for children having received combined DTP and OPV vaccinations, the case fatality ratio (CFR) being 0.29 (95% confidence interval (CI) 0.11-0.77). Even if children fleeing the hospital were assumed to have died shortly after leaving the hospital, the case fatality would still be lower for children having received OPV only (CFR = 0.41; (95% CI 0.20-0.81)). The tendency was similar for children hospitalised with pneumonia, diarrhoea, and presumptive malaria. Control for background factors had no impact on the estimate. In areas with high mortality, OPV administered alone may have non-specific beneficial effects or DTP may have a negative effect for children who had received both DTP and OPV.     

Nasal antibody response to mumps virus after vaccination and natural infection.

Nasopharyngeal secretions and sera were collected during an epidemic of mumps in a semi-closed institution. None of the children who received live attenuated mumps vaccine 5 months previously developed any symptoms of mumps. Neutralizing and IgA antibodies against mumps virus were measured by the peroxidase-antiperoxidase method and the fluorescent antibody to membrane antigen method, respectively. The immune responses in nasopharyngeal secretions and serum were studied in four groups (apparently infected, non-apparently infected, non-infected and vaccinated). We found that IgA, which has neutralizing activity, was produced after vaccination as well as after natural infection. It is suggested that local antibody induced by vaccination may contribute to protection against the mumps virus.     

Salivary antibody response to vaccination with meningococcal A/C polysaccharide vaccine in previously vaccinated and unvaccinated Gambian children

Development of salivary antibodies at the age of 4 or 5 years to group A and C meningococcal polysaccharides (MenA/C PS) was studied among Gambian children, who had received MenA/C conjugate or PS vaccine in infancy. There was also a control group of 64 age matched children. IgG, IgA, and secretory Ig concentrations were measured by enzyme immuno assay. MenA/C PS vaccine induced antibodies both in previously vaccinated and unvaccinated children. The previous vaccination had not induced long lasting IgA-mediated memory. IgA antibodies were secretory, and most of IgG was serum derived. The IgG salivary response seen was similar to the serum response.     

Measles in Tanzania: antibody response in children after vaccination and antibody state of mothers and newborns

The antibody response to attenuated live measles vaccines was studied in two groups of 29 (A) and 53 (B) African children. In group A 22 sera and in group B 34 sera showed no pre-immunization haemagglutination inhibition (HI) titres. Vaccination resulted in seroconversion in 64 and 85% of groups A and B, respectively. The difference in antibody response between the two groups could be traced to children in the age group seven to eight months, where seroconversion was absent in 67% of group A children and in 0% of group B children. Antibody levels were studied in 234 mothers and their newborns. In 131 serum pairs the antibody levels of mother and child were similar. 78 (33%) of mothers showed a higher titre and 25 (11%) a lower titre than their babies. All newborns except one and all mothers except one possessed antibody titres above 10. Children in the age groups seven to eight months and nine to ten months showed antibody in 12 and 7%, respectively. Over 90% of these children had not been infected in the first ten months of life.     

Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

BackgroundOral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated.MethodsIn urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea.ResultsCampylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (−0.08 change in log titer per tenfold increase in quantity; P = 0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64–0.96; P = 0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05–1.71; P = 0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity.ConclusionIn this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses.ClinicalTrials.gov Identifier: NCT01375647.     

Supplemental measles vaccine antibody response among HIV-infected and -uninfected children in Malawi after 1- and 2-dose primary measles vaccination schedules

BackgroundThe long-term antibody response to measles vaccine (MV) administered at age 6 months with or without subsequent doses is not well documented.MethodsMeasles serum antibody responses were evaluated after a supplemental dose of measles vaccine (sMV) administered at a median age of 20 months among Malawian children who had previously received 2 doses of measles vaccine (MV) at ages 6 and 9 months (HIV-infected and random sample of HIV-uninfected) or 1 dose at age 9 months (random sample of HIV-uninfected). We compared measles antibody seropositivity between groups by enzyme linked immunoassay and seroprotection by plaque reduction neutralization geometric mean concentrations.ResultsOf 1756 children enrolled, 887 (50.5%) received a sMV dose following MV at 9 months of age and had specimens available after sMV receipt, including 401 HIV-uninfected children who received one MV dose at 9 months, 464 HIV-uninfected and 22 HIV-infected children who received two doses of MV at ages 6 and 9 months. Among HIV-uninfected children, protective levels of antibody were found post sMV in 90–99% through ages 24–36 months and were not affected by MV schedule. Geometric mean concentration levels of measles antibody were significantly increased post-sMV among those HIV-uninfected children previously non-responsive to vaccination. Among HIV-infected children, the proportion seroprotected increased initially but by 9 months post-sMV was no higher than pre-sMV.ConclusionsOur findings support early 2-dose MV to provide measles immunity for young infants without risk of interference with antibody responses to subsequent MV doses administered as part of SIAs.     

Lack of association between intussusception and oral polio vaccine in Cuban children

Two exploratory investigations found an increased risk of intussusception after oral polio vaccine (OPV). A large, national, population-based study was undertaken in Cuba to investigate a possible association. Three hundred and thirty-five cases of intussusception in children under 2 years of age occurring in 1995–2000 were identified and their OPV records retrieved. The relative incidence (RI) of intussusception in defined periods up to 42 days after OPV in children under 1 year was estimated using the self-controlled case series method, controlling for age and season. The RI was not significantly raised in any of the time intervals examined within the 0–42 day period after OPV. For the period 0–42 days as a whole the RI was 1.11, 95% CI 0.74–1.67. This study does not support the hypothesis that OPV causes intussusception.     

Lack of viraemia and limited antibody response of dengue virus immune rhesus monkeys after vaccination with DEN-2/S-1 vaccine

A dengue-2 live virus vaccine was tested in monkeys immune to heterologous dengue serotypes to determine if, as with wild DEN-2 virus, antibody-enhanced viraemia and seroconversion would occur. A low dose of 900 plaque-forming units (PFU) of the DEN-2/S-1 vaccine virus was inoculated subcutaneously into rhesus monkeys six months after they had received wild DEN-1, DEN-2 or DEN-3 viruses, and into non-immune monkeys. As previously reported for non-immune monkeys, there was little, if any, detectable vaccine viraemia in any of the groups of monkeys. There was no difference in seroconversion between the dengue heterologously immune (3/6) and non-immune (1/3) monkeys. These data indicated that (i) the vaccine virus may differ from the parent virus in the ability to complex with heterologous antibody and, thus, in the ability to infect Fc receptor bearing cells in monkeys; (ii) 10(3) PFU of vaccine virus is approximately the 50% infectious dose in monkeys as measured by seroconversion.     

A bivalent virus-like particle based vaccine induces a balanced antibody response against both enterovirus 71 and norovirus in mice

Noroviruses are the main cause of severe viral gastroenteritis, which results in estimated 200,000 deaths each year, primarily in children in the developing world. Genogroup II.4 (GII.4) strains are responsible for the majority of norovirus outbreaks. Enterovirus 71 (EV71), the leading causative agent of hand, foot and mouth disease, has recently been prevalent in Asia-Pacific regions, resulting in significant morbidity and mortality in young children. However, no vaccine is commercially available for either norovirus GII.4 or EV71. Recombinant virus-like particles (VLPs) derived from either GII.4 or EV71 have been shown to be promising monovalent vaccine candidates. In this study, we investigate the possibility to formulate a VLP-based bivalent vaccine for both norovirus GII.4 and EV71. The GII.4- and EV71-VLPs were produced in a baculovirus-insect cell expression system. A bivalent combination vaccine comprised of GII.4 and EV71 VLPs was formulated and compared with monovalent GII.4- and EV71-VLPs for their immunogenicity in mice. We found that the bivalent vaccine elicited durable antibody responses toward both GII.4 and EV71, and the antibody titers were comparable to that induced by the monovalent vaccines, indicating there is no immunological interference between the two antigens in the combination vaccine. More significantly, the bivalent vaccine-immunized mouse sera could efficiently neutralize EV71 infection and block GII.4-VLP binding to mucin. Together, our results demonstrate that the experimental combination vaccine comprised of GII.4 and EV71-VLPs is able to induce a balanced protective antibody response, and therefore strongly support further preclinical and clinical development of such a bivalent VLP vaccine targeting both norovirus GII.4 and EV71.     

Prenatal undernutrition, postnatal environments, and antibody response to vaccination in adolescence

BACKGROUND: Recently, researchers have considered the fetal and infant origins of several adult cardiovascular and metabolic diseases, but the implications of early events for immune function and infectious disease are unclear. OBJECTIVE: We investigated the association between prenatal undernutrition and immunocompetence in adolescence and hypothesized that intrauterine growth retardation is associated with a lower likelihood of mounting an adequate antibody response later in life. DESIGN: A subsample of one hundred three 14-15-y-olds was recruited from an ongoing longitudinal study in which data collection began while participants were in utero. A typhoid vaccine was given, and anti-typhoid antibodies were measured 2 wk and 3 mo later as a functional marker of immunocompetence. The likelihood of mounting an adequate antibody response was compared for adolescents who were small for gestational age or appropriate for gestational age at birth while controlling for a range of postnatal exposures. RESULTS: The predicted probability of mounting a positive antibody response for adolescents who were prenatally and currently undernourished was 0.32, compared with probabilities of 0.49-0.70 for adequately nourished adolescents (P = 0.023). Diarrhea in the first year of life (P = 0.009) and fast weight gain during the first 6 mo (P = 0.003) were also associated with a higher probability of response. CONCLUSIONS: These findings extend the concept of fetal and early infant programming of adult diseases to the immune system and suggest that early environments may have long-term implications for immunocompetence and infectious disease risk, particularly in developing countries.     

Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis

Since the 1940s, influenza vaccines are inactivated and purified virus or virus subunit preparations (IIV) administered by the intramuscular route. Since decades, attempts have been made to construct, as an alternative, attenuated live influenza vaccines (LIV) for intranasal administration. Presently, the most successful LIV is derived from the cold-adapted master strains A/Ann Arbor/6/60 (H2N2) and B/Ann Arbor/1/66 (AA-LIV, for Ann-Arbor-derived live influenza vaccine). It has been claimed that AA-LIV is more efficacious than IIV. In order to assess differences between the two vaccines with respect to systemic reactogenicity, antibody response, and efficacy, we performed a meta-analysis on eighteen randomised comparative clinical trials involving a total of 5000 vaccinees of all ages. Pooled odds ratios (AA-LIV versus IIV) were calculated according to the random effects model. The two vaccines were associated with similarly low frequencies of systemic vaccine reactions (pooled odds ratio: 0.96, 95% confidence interval: 0.74-1.24). AA-LIV induced significantly lower levels of serum haemagglutination inhibiting antibody and significantly greater levels of local IgA antibody (influenza virus-specific respiratory IgA assayed by ELISA in nasal wash specimens) than IIV. Yet, although they predominantly stimulate different antibody compartments, the two vaccines were similarly efficacious in preventing culture-positive influenza illness. In all trials assessing clinical efficacy, the odds ratios were not significantly different from one (point of equivalence). The pooled odds ratio for influenza A-H3N2 was 1.50 (95% CI: 0.80-2.82), and for A-H1N1, 1.03 (95% CI: 0.58-1.82). The choice between the two vaccine types should be based on weighing the advantage of the attractive non-invasive mode of administration of AA-LIV, against serious concerns about the biological risks inherent to large-scale use of infectious influenza virus, in particular the hazard of gene reassortment with non-human influenza virus strains.