Indicators of immunity in children vaccinated with live poliomyelitis vaccine]

Serological examination of 1057 children, residents of Leningrad, vaccinated with poliomyelitis vaccine at the appropriate calendar dates according to the scheme, showed the presence of antibodies to the polioviruses in 81.5-99.1% of the cases. There were more serologically negative children against the virus type III, and much less--against the virus type II. The value of the mean geometrical titres somewhat decreased with the advance of the children's age and the time lapse after the vaccination and revaccination. The greatest antibody titres determined were against the poliovirus type II, and the least--against type III. No antibodies against the viruses of types I and III were revealed in case of deficiency against the poliovirus type II. The number of children with the absence of antibodies against the poliovirus of all the types was insignificant.     

Neuraminidase-Inhibiting Antibody Is a Correlate of Cross-Protection against Lethal H5N1 Influenza Virus in Ferrets Immunized with Seasonal Influenza Vaccine

In preparing for the threat of a pandemic of avian H5N1 influenza virus, we need to consider the significant delay (4 to 6 months) necessary to produce a strain-matched vaccine. As some degree of cross-reactivity between seasonal influenza vaccines and H5N1 virus has been reported, this was further explored in the ferret model to determine the targets of protective immunity. Ferrets were vaccinated with two intramuscular inoculations of trivalent inactivated split influenza vaccine or subcomponent vaccines, with and without adjuvant, and later challenged with a lethal dose of A/Vietnam/1203/2004 (H5N1) influenza virus. We confirmed that vaccination with seasonal influenza vaccine afforded partial protection against lethal H5N1 challenge and showed that use of either AlPO₄ or Iscomatrix adjuvant with the vaccine resulted in complete protection against disease and death. The protection was due exclusively to the H1N1 vaccine component, and although the hemagglutinin contributed to protection, the dominant protective response was targeted toward the neuraminidase (NA) and correlated with sialic acid cleavage-inhibiting antibody titers. Purified heterologous NA formulated with Iscomatrix adjuvant was also protective. These results suggest that adjuvanted seasonal trivalent vaccine could be used as an interim measure to decrease morbidity and mortality from H5N1 prior to the availability of a specific vaccine. The data also highlight that an inducer of cross-protective immunity is the NA, a protein whose levels are not normally monitored in vaccines and whose capacity to induce immunity in recipients is not normally assessed.     

Cross‐reactive antibody response to the pandemic A (H1N1) 2009 influenza virus induced by vaccination with a seasonal trivalent influenza vaccine: a longitudinal study of three influenza seasons in Japan

The cross‐reactivity of antibody to the swine‐origin pandemic influenza A (H1N1) 2009 virus induced by vaccination with a seasonal trivalent influenza vaccine was studied. Paired sera from a cohort of adult volunteers vaccinated with a trivalent seasonal influenza vaccine every year from 2006 to 2008 were collected each year and tested by hemagglutination inhibition (HI) for antibody against the pandemic influenza A (H1N1) 2009 virus. There was little increase in the geometric mean titer overall; a slight increase was detected in the sera obtained in the 2007–2008 season but not in the other two seasons. The proportion of individuals with HI antibody titers ≥ 1:40 did not change significantly from year to year. These results indicate that cross‐reactivity of the antibodies induced by a trivalent seasonal vaccine to the pandemic influenza A (H1N1) 2009 virus is marginal.     

Evaluation of poliovirus antibody titers in orally vaccinated semi‐captive chimpanzees in Uganda

Background To understand immunological responses in chimpanzees vaccinated with live‐attenuated vaccine (oral polio vaccine; OPV), serum neutralizing antibodies against poliovirus types 1, 2, and 3 were investigated over time. Methods The neutralizing antibody titers against poliovirus types 1, 2, and 3 were determined by microneutralization test using 100 ID₅₀ of poliovirus types 1, 2, and 3 (Sabin strains). Results Neutralizing antibodies against poliovirus types 1, 2, and 3 were detected in 85.7%, 71.4%, and 65% of the serum from 42 chimpanzees tested 9 years post‐vaccination. The neutralizing antibody titers in chimpanzees were similar to the documented levels in human studies as an indicator of vaccine efficacy. Conclusions This study reveals persistence of neutralizing antibodies in chimpanzees for at least 9 years after vaccination with OPV. This first study in chimpanzees provides useful information for the evaluation of the success of vaccination with OPV in other captive apes.     

Early kinetics of antibody response to inactivated influenza vaccine

The aim was to examine the rapidity of haemagglutination inhibiting (HI) antibody response induced by immunization with a current inactivated trivalent influenza vaccine. Five to six sequential serum samples collected in autumn 1992 from each of 68 vaccinees in three age groups were studied for HI antibodies to ten influenza virus strains representing vaccine and epidemic viruses. Geometric mean titres, response rates and protection rates are presented. Response rates of > 70% were overall, but not until two weeks after the vaccination. Significant two- and four-day post-vaccination antibody responses were detected only occasionally. In previously vaccinated persons, average antibody titres to some of the viruses decreased during the first days after the vaccination. In the subsequent samples, the titres remained lower than in persons who were not vaccinated against influenza in preceding years. Protection against influenza infection may be frequently developed not until two weeks after vaccination. This has relevance to prophylactic administration of amantadine and rimantadine when an influenza A outbreak is imminent and the vaccination is late.     

Persistence of influenza serum antibodies in humans following immunization with a bivalent A/Victoria and A/New Jersey vaccine.

The persistence of serum antibodies 1 year after immunization with a bivalent vaccine containing recombinant viruses that were antigenically identical with A/Victoria/3/75 (H3N2) and A/New Jersey/8/76 (Hsw1N1) viruses was measured in 128 persons aged 18 to 65 years. Serum samples were tested with the hemagglutination inhibition assay against the two vaccine antigens and against A/Texas/1/77 (H3N2) and A/USSR/90/77 (H1N1) viruses. Prior to vaccination 56% and 79% of the participants had been found to be seronegative to A/Victoria and A/New Jersey antigens respectively; the geometric mean antibody titres were low (1:5 to 1:11) except in persons aged 51 to 65 years, whose mean titre of antibody to the A/New Jersey antigen was 1:23, and persons aged 26 to 35 years, whose mean titre of antibody to the A/USSR antigen was 1:25. By 3 weeks after vaccination 85% of the seronegative persons had a fourfold or greater rise in titres of antibodies to the viruses in the vaccine, and 70% had a fourfold increase in titre of antibody to the A/Texas antigen. Of the persons aged 26 to 35 years (seronegative and seropositive) 68% had a fourfold or greater increase in titre of antibody to the A/USSR antigen. There was no change in the mean titres of 19 unvaccinated control subjects during the observation period. At 6 and 12 months after vaccination the titres of antibodies to the A/Victoria and A/New Jersey antigens had declined moderately in all age groups from those observed 3 weeks after vaccination. The rate of decline was similar for the various antibodies except that to the A/USSR antigen in persons 26 to 35 years of age, in whom the decline was much slower.     

Excretion of attenuated polioviruses in children vaccinated with live oral poliovirus vaccine

The excretion of attenuated polioviruses was studied in a group of nursery children vaccinated with 105TCD50 of each type of virus. The primovaccinated children were found to excrete type 1 poliovirus for 8 weeks, type 2 for 11 weeks after the vaccination with the type 1 + 2 bivaccine. Poliovirus type 1 as eliminated by 78% and type 2 by 98% of the vaccinees. The separately administered type 3 was detectable for 6 weeks and was isolated from 100% of the vaccinees. The highest per cent of children with type 1 excretion positivity was recorded at week 5, with type 2 positivity at week 1 and with type 3 positivity at week 2. The poliovirus excretion peaked early after the vaccination, the titres of the poliovirus type 2 were the highest. The children revaccinated next year with the type 1 + 2 bivaccine eliminated the respective types of virus 1 - 2 weeks; type 3 poliovirus was detectable for 6 weeks after revaccination and was excreted by the highest per cent of vaccines. The contact infections caused by the attenuated polioviruses developed in 9 from 22 children vaccinated previously. The excretion of polioviruses did not last longer than 1 week. The contact infections were most frequently caused by the poliovirus type 2. The examined children, particularly those vaccinated previously, turned out to excrete also other enteroviruses identified as Coxsakieviruses B 4 and B 5 and Echovirus 21. In the primovaccinated these viruses were isolated only from those with the negative excretion of polioviruses.     

The Effect of Age and Recent Influenza Vaccination History on the Immunogenicity and Efficacy of 2009–10 Seasonal Trivalent Inactivated Influenza Vaccination in Children

Background

There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV) may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6–8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.

Methods and Findings

We conducted a randomized controlled trial of 2009–10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1) and A(H3N2) particularly in children 9–17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6–8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6–8 y of age regardless of vaccination history.

Conclusions

Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.     

Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus

Background

The “gold standard” for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine.

Methods

199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation.

Results

An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4β7⁺ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4β7⁺ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7⁺ IgA^- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus.

Discussion

Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program.     

Comparative immunogenecity of foot and mouth disease virus antigens in FMD-haemorrhagic septicaemia combined vaccine and FMD vaccine alone in buffalo calves

Humoral immune response was evaluated by monitoring the serum antibody titres and virus specific IgM titres against Foot and Mouth Disease (FMD) virus antigens in serum samples obtained from different groups of calves inoculated with combined vaccine or FMD vaccine alone, on 0, 7, 14, 21, 28, 42 and 56 days post-vaccination (DPV). The cellular immune response was monitored by MTT based lymphoproliferation in peripheral blood mononuclear cell cultures. Higher liquid phase blocking (LPB) ELISA antibody titres were observed in calves receiving combined vaccine as compared to calves immunized with FMD vaccine alone with the peak titres in both the groups obtained on 21 days post-vaccination. However, the virus specific IgM titres were significantly higher in group of calves inoculated with combined vaccine than FMD vaccine alone. The lymphoproliferative responses against FMDV types O, A22 and Asia 1 in the groups receiving combined vaccine and FMD vaccine alone started increasing gradually after day 14 and reached peak levels on 28 DPV followed by a gradual decline subsequently. The group receiving combined vaccine showed higher proliferative responses on in vitro stimulation with FMD virus type O, whereas, with FMD virus type Asia 1, the responses were significantly higher on 14 and 21 DPV as compared to the group immunized with FMD vaccine alone. However, in the group receiving combined vaccine, the responses on in vitro stimulation with FMD virus type A22 were significantly higher than FMD vaccine alone group on all DPV except on 42 DPV.     

Excretion of live attenuated polioviruses in the faeces of orally vaccinated children. Comparison of two immunization schedules

The excretion of live, attenuated poliovirus vaccine strains was determined in the feces of Prague Infants home children given 10(5) PFU of type 1 and 2 and 2.10(5) PFU of type 3 vaccine in a routine annual mass campaign. The first two faeces specimens examined in each vaccinee prior to immunization were negative for the virus. A total of 476 stool specimens were collected from 37 children at weekly intervals for a period of 18 weeks. The presence of type 1 poliovirus in the faeces of children given monovalent type 1 vaccine was detectable for 9 weeks, with a maximum in first week, and the virus was isolated in 74.2% of vaccinees. The timing of bivalent type 2 and type 3 vaccine was 9 weeks after monovalent type 1 immunization. The excretion of these two types of poliovirus was found to persist for at least 6 weeks. Type 2 poliovirus was isolated in all vaccinees, type 3 in 70.4% of children. The highest percentage of children excreting type 2 poliovirus was recorded in the first week, the excretion of type 3 peaked three weeks after bivaccine administration. The excretion peaks were reached relatively early postvaccination, with type poliovirus reaching the highest titre per 1 g of faeces. After revaccination (one year later) with monovalent type 1 vaccine, the vaccine strain of type 1 poliovirus could be detected for 6 weeks and was present in the highest percentage of positive stool samples.(ABSTRACT TRUNCATED AT 250 WORDS)     

Polio antibody outfit of newborns and infants born after 20 years of mass vaccination with live poliovaccine

Antibodies against type 1 and 2 poliovirus were tested in 250 infants and against type 3 poliovirus in 341 infants aged 0-13 months to compare the polio antibody outfit of newborns and infants born to three groups of mothers: (a) nonvaccinated, above 35 years of age; (b) vaccinated with attenuated poliovirus but having had chance of contact with wild poliovirus during childhood, age 22-35 years, and (c) vaccinated but not having had contact with wild poliovirus, below 22 years of age. Over 90% of newborns had specific neutralizing antibodies against all three poliovirus types. With increasing infant age the percentage of antibody-positive infants decreased: by age 9-11 months only 46%, 27% and 14% of infants displayed antibodies to polio-virus types 1, 2 and 3, respectively. Geometric mean titres decreased accordingly. Differences between infants born to mothers of the above three groups were nonsignificant: the results obtained suggest that future newborns will also possess satisfactory levels of antibodies acquired from mothers who have only had contact with attenuated vaccine poliovirus.     

Evaluation of live trivalent vaccine of measles AIK-C strain, mumps Hoshino strain and rubella Takahashi strain, by virus-specific interferon-gamma production and antibody response

A trivalent measles-mumps-rubella live virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was evaluated in 229 children, aged 1 to 5 years. The vaccine induced a high seroconversion rate: 221 (98.7%) out of 224 subjects initially seronegative for measles virus, 167 (93.3%) out of 179 initially seronegative for mumps virus, and 212 (99.1%) out of 214 initially seronegative for rubella virus. It also induced a sufficient cellular immunity against each of the three viruses in over 90% of the subjects, as judged by virus-specific interferon-gamma (IFN-gamma) production. Virus-specific IFN-gamma production was observed 10 days after vaccination by stimulation with measles virus and rubella virus and 14 days after vaccination by stimulation with mumps virus. Mumps-virus-specific IFN-gamma production was observed in 7 out of 12 recipients without seroconversion for mumps virus. And measles-virus-specific IFN-gamma production was demonstrated in one out of three recipients without seroconversion for measles virus. A significant correlation was observed between the serum antibody and IFN-gamma production six weeks after vaccination for measles virus (r = 0.201, P less than 0.01) and for mumps virus (r = 0.174, P less than 0.05) but not for rubella virus (r = -0.045, P less than 0.05). The incidence of febrile reactions of greater than or equal to 37.5 C was quite low, 14.4%, and that of greater than or equal to 39 C occurred in only 1.3% of the recipients. These results suggested that the trivalent vaccine induced sufficient humoral and cellular immunity and yet resulted in no more untoward reaction than observed from the measles vaccine alone.     

Safety, efficacy and effectiveness of cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine in adults and children.

Studies in children and adults revealed cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine (CAIV-T) to be well accepted, well tolerated and highly protective against culture-confirmed influenza, and to provide significant health benefits. A 2 year, multicentre, double-blind, placebo-controlled efficacy field trial of CAIV-T in children aged 15-71 months with annual re-immunization revealed the vaccine to be highly protective against culture-confirmed influenza. Vaccine induced serum and secretory antibodies in vaccinated children. Overall, during 2 years of study, vaccine was 92% protective against culture-confirmed influenza. During the second year of study the vaccine was 86% protective against influenza A/Sydney/5/97-like virus, a significantly drifted strain not well matched to the vaccine. Antibody studies on children given CAIV-T revealed that high titres of cross-reacting antibodies to influenza A/Sydney/5/97 were induced with vaccination by live attenuated influenza A/Wuhan/359/95-like vaccine. Effectiveness measures revealed significant reductions in febrile illness (21% reduction in year 1, 19% reduction in year 2), febrile otitis media (33% reduction in year 1, 16% reduction in year 2) and associated antibiotic use among vaccinated children compared with placebo recipients. In adults, vaccination with CAIV-T resulted in protection during experimental challenge with virulent wild-type viruses. An effectiveness trial in adults demonstrated significant benefits of CAIV-T vaccine (28% reduction in days of missed work for febrile upper respiratory illness days with associated 45% reduction in days taking antibiotics). General use of CAIV-T has the potential to significantly reduce the impact of influenza in children and adults.     

The antibody response of seronegative infants to inactivated poliovirus vaccine of enhanced potency

The immunogenic efficacy of inactivated poliovirus vaccine of enhanced potency (IPV-E), containing 40, 8 and 32 D-antigen units of types 1, 2 and 3, respectively, was evaluated in tritypic seronegative infants. Eighty infants aged six to 45 weeks, with no antibody detectable at a 1 : 4 dilution, were given two doses of a quadruple vaccine containing diphtheria-pertussis-tetanus (DPT) vaccine and IPV-E at intervals of four weeks (37 infants, group 1) or eight weeks (43 infants, group 2) between doses. All infants of group 2 responded with antibody to the three types of polioviruses. In group 1, all responded to types 1 and 3 antigens but only 36 responded to type 2. Antibody titres were higher in infants immunized at eight week than at four week intervals. Thus, two doses of IPV-E, especially when given eight weeks apart, are sufficient for primary immunization against poliomyelitis. If DPT vaccine of enhanced potency is combined with IPV-E, two doses of such a quadruple vaccine may be sufficient for primary immunization against four diseases; this possibility deserves evaluation.     

Effect of prior vaccination with a seasonal trivalent influenza vaccine on the antibody response to the influenza pandemic H1N1 2009 vaccine: a randomized controlled trial

Vaccination with the non-adjuvanted split-virion A/California/7/2009 influenza vaccine (pandemic H1N1 2009 vaccine) began in October 2009 in Japan. The present study was designed to assess the effect of prior vaccination with a seasonal trivalent influenza vaccine on the antibody response to the pandemic H1N1 2009 vaccine in healthy adult volunteers. One hundred and seventeen participants aged 22 to 62 were randomly assigned to two study groups. In Group 1 (the priming group), participants were first vaccinated with the seasonal trivalent influenza vaccine followed by two separate one-dose vaccinations of the pandemic H1N1 2009 vaccine, whereas in Group 2 (the non-priming group), the participants were first vaccinated with one dose of the pandemic H1N1 2009 vaccine, followed by simultaneous vaccination of the seasonal trivalent vaccine and the second dose of the pandemic H1N1 2009 vaccine. The participants in Group 2 had a seroprotection rate (SPR) of 79.7% and a seroconversion rate (SCR) of 79.7% in the hemagglutination-inhibition test after the first dose of the pandemic H1N1 2009 vaccine, indicating that the pandemic H1N1 2009 vaccine is sufficiently immunogenic. On the other hand, the participants of Group 1 had a significantly weaker antibody response, with a SPR of 60.8% and a SCR of 58.5%. These results indicate that prior vaccination with the seasonal trivalent influenza vaccine inhibits the antibody response to the pandemic H1N1 2009 vaccine. Therefore, the pandemic H1N1 2009 vaccine should be administered prior to vaccination with the seasonal trivalent influenza vaccine.     

A single-blind, placebo-controlled comparison of the reactivity and antigenicity of trivalent oral poliomyelitis vaccine prepared in monkey kidney or human diploid cell substrates

Vaccination with a single dose of trivalent oral poliomyelitis vaccine elicited fourfold or greater antibody responses to one or more poliomyelitis virus types in 59% of volunteers (16/27) receiving vaccine prepared from virus grown in monkey kidney cells and in 69% of volunteers (16/23) receiving vaccine prepared from virus grown in MRC5 human diploid cells. Type for type the antibody titres and percentages of volunteers responding to the two vaccines were broadly equivalent. The clinical reactivities of both vaccines were similar to that of a placebo in terms of the overall incidence, duration and severity of reactions. The nature of the reactions observed did, however, vary, in that headaches were more frequently reported by recipients of vaccine prepared from virus grown in monkey kidney cells. This difference was not, however, statistically significant.     

A new generation of modified live-attenuated avian influenza viruses using a two-strategy combination as potential vaccine candidates

In light of the recurrent outbreaks of low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI), there is a pressing need for the development of vaccines that allow rapid mass vaccination. In this study, we introduced by reverse genetics temperature-sensitive mutations in the PB1 and PB2 genes of an avian influenza virus, A/Guinea Fowl/Hong Kong/WF10/99 (H9N2) (WF10). Further genetic modifications were introduced into the PB1 gene to enhance the attenuated (att) phenotype of the virus in vivo. Using the att WF10 as a backbone, we substituted neuraminidase (NA) for hemagglutinin (HA) for vaccine purposes. In chickens, a vaccination scheme consisting of a single dose of an att H7N2 vaccine virus at 2 weeks of age and subsequent challenge with the wild-type H7N2 LPAI virus resulted in complete protection. We further extended our vaccination strategy against the HPAI H5N1. In this case, we reconstituted an att H5N1 vaccine virus, whose HA and NA genes were derived from an Asian H5N1 virus. A single-dose immunization in ovo with the att H5N1 vaccine virus in 18-day-old chicken embryos resulted in more than 60% protection for 4-week-old chickens and 100% protection for 9- to 12-week-old chickens. Boosting at 2 weeks posthatching provided 100% protection against challenge with the HPAI H5N1 virus for chickens as young as 4 weeks old, with undetectable virus shedding postchallenge. Our results highlight the potential of live att avian influenza vaccines for mass vaccination in poultry.     

Properties of poliovirus strains isolated over the period 1969-1978 from the main municipal sewerage system of the city of Prague

Biological properties (rct marker and antigenic relatedness) were compared in vaccine prototype strains and in 62 poliovirus strains isolated during a period 1969-1978 from the main municipal sewerage system of the City of Prague. None of the strains isolated from the municipal sewerage showed biologic properties that would fully differ from those observed in vaccine-derived strains. The strains detected very late postvaccination (after about a year) showed a lesser extent of changes than strains isolated earlier after vaccination. The most frequent changes were recorded in type 2 strains, less frequent in type 3 strains and the least frequency of changes was found in type 1 strains. To facilitate comparisons of these changes in dependence on time of postvaccination virus excretion a supporting evaluation criterion has been developed to help express the dynamics of changes in the isolated poliovirus strains. The recorded degree of the dynamics of changes was highest in type 2 strains, lower in type 3 strains and lowest in type 1 strains. The dynamics of changes detected in strains of various types was not always constant in the course of years: in a given year (or in a period of several years) changes occurred always in strains of the same serologic type, whereas strains of the other two types changed only insignificantly during the respective period.     

Preexisting immunity to poliovirus does not impair the efficacy of recombinant poliovirus vaccine vectors

Recombinant viruses are attractive candidates for the development of novel vaccines. A number of viruses have been engineered as vaccine vectors to express antigens from other pathogens or tumors. Inoculation of susceptible animals with this type of recombinant virus results in the induction of both humoral and cellular immune responses directed against the foreign antigens. A general problem to this approach is that existing immunity to the vector can diminish or completely abolish the efficacy of the viral vector. In this study, we investigated whether poliovirus recombinants are capable of inducing effective immunity to the foreign antigen in previously vaccinated animals. Antipoliovirus immunity was induced in susceptible mice by intraperitoneal immunization with live poliovirus. Immunized mice developed antibodies directed against capsid proteins that effectively neutralized poliovirus in vitro and protected animals from a lethal challenge with a high dose of pathogenic poliovirus. To test whether preexisting immunity reduces the efficacy of vaccination with recombinant poliovirus, immunized mice were inoculated with a recombinant poliovirus expressing the C-terminal half of chicken ovalbumin (Polio-Ova). Animals developed ovalbumin-specific antibodies and cytotoxic T lymphocytes (CTL). While the antibody titers observed in preimmune and naive mice were similar, the overall CTL response appeared to be reduced in preimmune mice. Importantly, vaccination with Polio-Ova was able to effectively protect preimmune mice against lethal challenge with a tumor expressing the antigen. Thus, preexisting immunity to poliovirus does not compromise seriously the efficacy of replication-competent poliovirus vaccine vectors. These results contrast with those observed for other viral vaccine vectors and suggest that preexisting immunity does not equally affect the vaccine potential of individual viral vectors.