Immune response to an intercalated enhanced inactivated polio vaccine/oral polio vaccine programme in Israel: impact on the control of poliomyelitis

A combined enhanced inactivated polio vaccine (EIPV) and oral polio vaccine (OPV) programme was introduced in Israel in 1990, with the purpose of providing a solution to the persistent polio morbidity in spite of a 30 year long OPV programme. The schedule comprised two doses of EIPV administered at the age of 2 and 4 months, intercalated with two doses of OPV at 4 and 6 months, followed by a reinforcing dose with the two vaccines simultaneously administered at 12 months. The 5-year evaluation of the programme included: the assessment of clinical suspicions of polio, early immune response in successive cohorts administered the new schedule, dynamics of the immune profile in a cohort followed up to the age of 5, and monitoring of wild poliovirus excretion in sewage specimens collected in 25 permanent sites throughout Israel as well as from the Palestinian Authority. No paralytic polio cases associated with a wild or vaccinal poliovirus strain were detected since the introduction of the programme. At the age of 4 months, one week after administration of the second EIPV and first OPV dose, 100% seropositivity and high geometric mean titres (GMTs) of neutralizing antibody (NA) to the three vaccinal and to the wild poliovirus type 1, responsible for the 1988 polio outbreak, were observed. No change in percent of seropositivity occurred between the age of 6 and 12 months. Thirty days after the IPV and OPV reinforcing doses, GMTs to each of the four poliovirus strains were > or = 3037. Up to the age of 5, the seropositivity was unchanged. After a 2.5-10-fold decline in the first year following the completion of the programme, GMTs to the three vaccinal and the wild poliovirus strain levelled off at rather high values, considered protective. Between 1990 and 1995, 16 wild poliovirus type 1 strains were isolated in three separate episodes in Gaza Strip sewage and once only in one Israeli site very close to Gaza City. The rapidly established, high and persistent NA titre to the vaccinal and wild poliovirus strains and the presence of immunological memory are indicative of high individual protection throughout the first 5 years of life. The only one-time introduction, without circulation, of a wild poliovirus strain in a single Israeli settlement suggests community protection. The intercalated programme offers a contribution to polio eradication by providing a solution to the primary and secondary failure associated with OPV, as well as to the control of vaccine-associated paralytic poliomyelitis.     

Parental knowledge and choice regarding live and inactivated poliovirus vaccines

BACKGROUND: Concern about the 8 to 10 cases per year of vaccine-associated paralytic poliomyelitis caused by the live oral poliovirus vaccine (OPV) has led to revised guidelines for immunization of children in the United States. The use of inactivated poliovirus vaccine (IPV) at 2 and 4 months of age could require administration of 3 injections per visit until combination products are available. OBJECTIVE: To determine parents' knowledge of poliovirus vaccines and the choices they would make between IPV and OPV. METHODS: Parents of 240 children aged 2 weeks to 18 months under the care of 10 private pediatricians in the Baltimore, Md, metropolitan area were interviewed prior to the announcement of revised advisory committee guidelines. RESULTS: The majority (62.5%) of respondents were not aware that 2 poliovirus vaccines are available. After reviewing standardized information about the vaccines and 2 alternate schedules, most (75%) parents would consult someone (primarily their physician) before making a final choice of a vaccine schedule. If parents made the choice without consulting anyone else, 61.3% would choose to have their child receive IPV and 3 injections per visit as compared with an all-OPV schedule and 2 injections per visit. Inactivated poliovirus vaccine was preferred by most parents because it would reduce the risk for vaccine-associated paralytic poliomyelitis. Oral poliovirus vaccine was preferred by 37.9% of parents primarily because it was given orally. If the number of injections at each visit was the same for both vaccines, 76.3% of parents would choose the IPV schedule, and if the number of injections was reduced to 2 by combining IPV with another vaccine, 87.9% of parents would choose IPV. CONCLUSION: The number of injections per visit is an important issue, but a majority of parents would choose to have their children receive extra injections to prevent the low risk for vaccine-associated paralytic poliomyelitis.     

Childhood immunizations: position on the enhanced inactivated poliovirus vaccine and live attenuated oral poliovirus vaccine dilemma

Recent review of the polio vaccines (live attenuated oral poliovirus vaccine [OPV] and enhanced inactivated poliovirus vaccine [eIPV]) for children has generated much debate between infectious disease experts and public health officials. Poliomyelitis was a common medical condition in the 1940s and 1950s, and the success of OPV in eradicating poliomyelitis from the United States and even the Western hemisphere cannot be disputed. However, the adverse condition of vaccine-associated paralytic poliomyelitis (VAPP) has been reported in eight to nine cases per year as a result of exclusively using OPV in the United States. The dilemma has been how to continue the elimination of wild-type poliovirus paralytic poliomyelitis in the United States and worldwide while minimizing the occurrence of VAPP. Clinical trials have supported that eIPV and OPV provide similar protection for humoral immunity. However, OPV provides superior gastrointestinal immunity, which is a public health benefit for vulnerable populations. Recommendations among experts have concluded that the sequential eIPV/OPV is the preferred schedule, with eIPV only or OPV only as alternative equally acceptable schedules. Therefore, factors such as cost, compliance, and access to health care must be considered by parents and providers when selecting a polio vaccine regimen, especially among underserved populations.     

Substance P- and calcitonin gene-related peptide-containing nerve fibers in the nasal mucosa of chronically hypoxic rats

Changes made in 1997 and 1998 in the U.S. childhood immunization schedule are discussed, with a focus on the use of poliovirus, pertussis, and combination vaccines. Oral poliovirus vaccine (OPV), the vaccine of choice for all four doses in the polio immunization series since 1962, can cause vaccine-associated paralytic poliomyelitis (VAPP). The inactivated poliovirus vaccine (IPV) has not been associated with VAPP but must be administered by injection and provides inferior intestinal immunity. With the reduced threat of poliovirus importation into the United States, the risk of VAPP, although low, has become less acceptable. The Centers for Disease Control and Prevention accordingly recommended a shift from OPV to IPV in the childhood immunization schedule for the United States, effective January 1997. A sequential OPV and IPV series is recommended, but the schedule includes an OPV-only option, which may be preferred in order to avoid the required injections, and an IPV-only option, which is recommended for immunocompromised persons and their contacts. Concern over local and systemic reactions associated with whole-cell pertussis vaccines, in addition to controversy over a possible relationship between the whole-cell vaccine and neurologic damage, has led to the development of new diphtheria and tetanus toxoids and acellular pertussis vaccine products for use in the diphtheria and tetanus toxoids and pertussis immunization series. Several combination products were licensed in 1997, and more are on the way. This will mean fewer inoculations for children. Increased use of IPV and acellular pertussis products could reduce the frequency of VAPP due to OPV and the local and systemic reactions associated with whole-cell pertussis vaccine.     

Comparative reactogenicity and immunogenicity of booster doses of diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine and diphtheria-tetanus-inactivated poliovirus vaccine in preadolescents

BACKGROUND: The changing epidemiology of pertussis in France has emphasized the need for booster vaccinations in adolescents. Although not previously recommended because of the high reactogenicity of whole cell pertussis in children older than 2 years old, the development of less reactogenic acellular pertussis vaccines means that this recommendation may be reconsidered. OBJECTIVES: Assessment of the reactogenicity and immunogenicity of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus (DTPa-IPV=Group 1) vaccine administered as the fifth dose in preadolescents in comparison with a commercial diphtheria-tetanus-inactivated poliovirus (DT-IPV) (Group 2) vaccine currently recommended for this age group. MATERIALS AND METHODS: An open, randomized study involving 115 healthy subjects ages 10 to 13 years previously vaccinated with 4 doses of diphtheria-tetanus-whole cell pertussis-IPV vaccines. Reactogenicity was assessed for 4 days postvaccination using diary cards. Immunogenicity based on antibody assays in sera taken before and 1 month postvaccination was evaluated for all vaccine antigen components. RESULTS: Both vaccines showed good tolerability, local and general reactogenicity being similar. For local reactions Group 1=88.1% and Group 2=86.8%, and for general reactions Group 1=40.7% and Group 2=47.2%. Headache was the most frequent general symptom with 27.1% for DTPa-IPV and 39.6% for DT-IPV. The incidence of fever was 5.1% with DTPa-IPV and 9.4% for DT-IPV. Good immune responses were obtained against all vaccine components. CONCLUSIONS: The inclusion of acellular pertussis did not significantly increase the reactogenicity of DTPa-IPV in comparison with the currently recommended DT-IPV vaccine when given as a fifth dose in preadolescents. To prevent recent resurgence of pertussis in France, this vaccine should be preferred as the booster dose of DTPa-IPV at 11 to 13 years of age as recently approved by the National Council of Hygiene of France.     

Valproic acid in prophylactic treatment of migraine

AIM: To determine whether an oral tetravalent rotavirus vaccine (RV-TV) can be safely coadministered with a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP/Hib) and oral poliovirus vaccine (OPV) to healthy infants without interfering with the immune responses to any of the component antigens. METHODS: Two hundred sixty-seven infants ages 2 to 3 months were randomly assigned in a double blind fashion to receive three doses of either placebo or RV-TV, each containing 4 x 10(5) plaque-forming units, concurrently with DTP/ Hib (Tetramune) and OPV at approximately 2, 4 and 6 months of age. Infants were followed for 5 days after each dose for the occurrence of adverse events and subsequently until 3 to 6 weeks after the third dose of RV-TV or placebo. Immune responses were assessed by measuring the postvaccination serum antibody titers to each component of DTP/ Hib and OPV at 3 to 6 weeks after the third dose. RESULTS: The percentage of infants who attained protective antibody titers and the distribution of antibody titers against diphtheria toxoid, tetanus toxoid and H. influenzae type b were not statistically different between RV-TV and placebo recipients. The distribution of antibody titers against different antigens of Bordetella pertussis (agglutinins, pertussis toxoid, filamentous hemagglutinin, fimbriae antigens and the 69-kDa outer membrane protein) was compared and no significant differences were found. The percentage of infants with detectable neutralizing antibodies against the three serotypes of poliovirus and the distribution of antibody titers was not statistically different between RV-TV and placebo recipients. There were no clinically meaningful differences in postvaccination reactions between RV-TV and placebo recipients. CONCLUSIONS: Three doses of RV-TV can be safely coadministered with three doses of DTP/ Hib and OPV without diminishing an infant's serum antibody responses to each component of these vaccines. Therefore RV-TV can be given at the standard childhood visits at 2, 4 and 6 months of age.     

Antibiotics: what''s new?

Until worldwide eradication of poliomyelitis is achieved, vaccination with poliovirus vaccines is the only means for providing population and individual immunity to polioviruses. The ACIP, AAP, and AAFP support the global poliomyelitis eradication initiative, and have recommended a transition policy that will increase use of IPV and decrease use of OPV during the next 3 to 5 years.     

A poliovirus-susceptible transgenic mouse model as a possible replacement for the monkey neurovirulence test of oral poliovirus vaccine

Two poliovirus-susceptible transgenic mouse (Tg PVR) strains, Tg1 and Tg21, were compared with the monkey test for their sensitivity to neurovirulence of live oral poliovirus vaccine (OPV). Intracerebral (i.c.) and intraspinal (i.s.) routes of inoculation were investigated to determine the most suitable combination of mouse strain and route. Evaluation of the mouse tests was performed using several indicators; clinical score and failure time were selected as the most efficient. Tg1 and Tg21 mice inoculated i.s. with type 2, and Tg21 mice inoculated i.s. with type 3 OPV were determined to be the most appropriate systems, whereas they are shown not to be suitable for type 1 OPV. The sensitivity of each of the two mouse models was at least equal to that of the monkey test, suggesting that these mouse systems might be considered as a potential replacement for the monkey test of OPV. However, more data are needed to establish regulatory criteria of acceptability for vaccine lots tested in Tg PVR mice. This is the first study conducted with Tg PVR mice with all three types of poliovirus vaccine preparations.     

Poliovirus vaccine options

As a result of the success of immunization, indigenous wild poliomyelitis has disappeared from the United States. Of 142 confirmed cases of paralytic poliomyelitis reported in the United States from 1980 to 1996, 134 were classified as vaccine-associated paralytic poliomyelitis (VAPP). Persons with VAPP have a disabling illness, and this has caught the attention of the lay media. The risk of VAPP is one case per 750,000 doses distributed for the first dose of oral poliovirus vaccine (OPV) and one case per 2.4 million doses of OPV distributed overall. Because of this risk, most parents prefer a vaccine schedule that starts with inactivated poliovirus vaccine (IPV), even though extra injections are required. IPV does not cause VAPP. New studies show that high immunization rates can be achieved in disadvantaged populations with a schedule starting with IPV. The American Academy of Family Physicians now recommends that the first two doses of poliovirus vaccine should be IPV; that is, either an all-IPV schedule or a sequential schedule of two doses of IPV followed by two doses of OPV. OPV is no longer recommended for the first two doses and is acceptable only under special circumstances, such as when parents do not accept the recommended number of injections.     

Potential use of poliovirus as a vector

The live attenuated Sabin strains of poliovirus have proven their efficacy at inducing a good humoral and secretory antibody response in humans. The extensive characterization of poliovirus neutralization antigenic sites and the atomic resolution of the three-dimensional structure of the viral capsid have enabled the use of the most stably attenuated poliovirus strain (the Sabin type 1 strain) as a vector for the presentation of short foreign antigenic domains in place of one of its own neutralization antigenic sites. The creation of such chimeras has been achieved by manipulating poliovirus infectious cDNA and transfecting the resulting chimeric cDNAs onto susceptible cell cultures. However, this epitope-presentation system has a limitation in terms of the sequence and size of the foreign domain that can be incorporated into the poliovirus capsid without disrupting virus viability. This has led to the construction of poliovirus hybrid genomes bearing insertions of longer heterologous sequences in place of part of the poliovirus structural genes. Upon transfection onto susceptible cells providing the poliovirus structural proteins in trans (e.g. cells previously infected with the Sabin 1 strain), stocks of encapsidated RNA replicons which expressed the foreign protein could be obtained. In addition, viable recombinant viruses bearing insertions of heterologous sequences at various places into the poliovirus genome without deleting poliovirus sequences have been reported. Potential applications of these chimeric and recombinant polioviruses in the engineering of new recombinant vaccines are discussed.     

Randomized comparison of early and late vaccination with inactivated poliovirus vaccine after allogeneic BMT

Forty-five adult HLA-matched sibling BMT recipients were randomized to receive inactivated poliovirus vaccine (IPV) at 6, 8 and 14 months (early group, n = 23) or at 18, 20 and 26 months after BMT (late group, n = 22). Ninety-five percent of the early group patients had protective antibody titres of > or = 4 to poliovirus type 1 (PV1), poliovirus type 2 (PV2) and poliovirus type 3 (PV3) by a microneutralization assay prior to the first vaccination, at 6 months after BMT. The corresponding proportion for the late group patients was only 67% at 18 months. The antibody responses 1 month after each of the three IPV doses were similar in the two vaccination groups, except that four-fold responses occurred more frequently after the first dose to PV2 and PV3 in the late group. All patients had a protective antibody titre to all poliovirus serotypes 1 and 22 months after the third vaccine dose, except one patient in the early group who lacked antibodies to PV3 at 22 months. Acute GVHD accelerated the decrease of poliovirus antibody titres prior to vaccination but had no influence on vaccination response. Chronic GVHD neither influenced the patient's ability to retain poliovirus antibodies prior to vaccination nor impaired responses to vaccinations. A vaccination schedule consisting of three IPV doses was equally immunogenic when started at 6 or 18 months after allogeneic BMT.     

Effect of diarrhea on the humoral response to oral polio vaccination

OBJECTIVE: The purpose of this study was to measure the effect of concurrent diarrheal illness on seroconversion to trivalent oral polio vaccine (OPV). METHODS: Six- to 16-week-old infants with acute diarrhea and age-matched controls received single doses of OPV at enrollment, 4 weeks after enrollment and 8 weeks after enrollment. Serum specimens were obtained at enrollment, before the second OPV dose and 4 weeks after the third OPV dose for measurement of antibody titers to polio virus by the microneutralization assay. RESULTS: Four weeks after the first OPV dose, the serologic responses to poliovirus types 2 and 3 in the case cohort were lower by 26 and 34%, respectively, than in the control cohort (P < 0.002 for both comparisons). Poliovirus type 2 and 3 geometric mean antibody titers in the diarrhea cohort were approximately 50% of the geometric mean antibody titers in the control cohort (235 (95% confidence interval (CI) 154 to 359) vs. 446 (95% CI 350 to 569) and 64 (95% CI 45 to 90) vs. 112 (95% CI 88 to 143), respectively, P < 0.01 for both comparisons). After the third OPV dose the seroconvertion rates to poliovirus types 2 and 3 each remained about 10% lower in the case cohort than in the control cohort, but the differences were not statistically significant. CONCLUSION: Concurrent acute diarrhea adversely affects seroconvertion rates of type 2 and 3 polioviruses among infants in Bangladesh receiving the first dose of trivalent OPV.     

Placental transfer of maternal poliovirus antibodies in full-term and pre-term infants

This study was designed to investigate the placental transfer of maternal poliovirus antibodies in full-term and pre-term infants. Two hundred healthy, Israeli born mothers and their infants, were enrolled immediately after birth. The study population comprised two groups: a full-term group of 150 mothers and their infants, and a pre-term group of 50 mothers and their infants (gestational age < 35 weeks). Maternal and umbilical cord blood samples were taken in all cases. Antibody titers against the three poliovirus serotypes and a polio virus type 1 strain that caused an outbreak in 1988 (epidemic strain 1) were measured by a microneutralization system. The proportion of individuals with protective titers against each of the poliovirus types tested was slightly lower in the infants compared with their mothers. When protection to all strains combined was tested, the difference between mothers and infants was significant (P < 0.05). Transplacental transfer to epidemic strain 1 was less effective--12% of the premature infants were not protected against it at birth. The geometric mean titers against poliovirus types 1, 3 and epidemic type 1 strain were significantly lower in the pre-term group than in the full-term group. In both the full-term and pre-term groups there were significant linear correlations between the maternal and neonatal antibody titers for each of the polio viruses tested. For all poliovirus types, the transfer of maternal antibodies to the full-term infant was significantly higher than the transfer of maternal antibodies to the pre-term infant (P < 0.001). Owing to diminished transfer of maternal antibodies, pre-term infants are at greater risk of poliovirus infection.     

Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization

Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine. Children were 1-4 years old at the time of vaccination. Most showed a good initial response to vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels. This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization. Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization. Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory.     

Influence of maternal antibodies on vaccine responses: inhibition of antibody but not T cell responses allows successful early prime-boost strategies in mice

The transfer of maternal antibodies to the offspring and their inhibitory effects on active infant immunization is an important factor hampering the use of certain vaccines, such as measles or respiratory syncytial virus vaccine, in early infancy. The resulting delay in protection by conventional or novel vaccines may have significant public health consequences. To define immunization approaches which may circumvent this phenomenon, experiments were set up to further elucidate its immunological bases. The influence of maternal antibodies on antibody and T cell responses to measles hemagglutinin (MV-HA) were analyzed following MV-HA immunization of pups born to immune or control BALB/c mothers using four different antigen delivery systems: live or inactivated conventional measles vaccine, a live recombinant canarypox vector and a DNA vaccine. High levels (> 5 log10) of maternal anti-HA antibodies totally inhibited antibody responses to each of the vaccine constructs, whereas normal antibody responses were elicited in presence of lower titers of maternal antibodies. However, even high titers of maternal antibodies affected neither the induction of vaccine-specific Th1/Th2 responses, as assessed by proliferation and levels of IFN-gamma and IL-5 production, nor CTL responses in infant mice. On the basis of these unaltered T cell responses, very early priming and boosting (at 1 and 3 weeks of age, respectively) with live measles vaccine allowed to circumvent maternal antibody inhibition of antibody responses in pups of immune mothers. This was confirmed in another immunization model (tetanus toxoid). It suggests that effective vaccine responses may be obtained earlier in presence of maternal antibodies through the use of appropriate immunization strategies using conventional or novel vaccines for early priming.     

MF59 adjuvant enhances antibody responses of infant baboons immunized with Haemophilus influenzae type b and Neisseria meningitidis group C oligosaccharide-CRM197 conjugate vaccine

The ability of the adjuvant MF59 to enhance the immunogenicity of polysaccharide-protein conjugate vaccines was investigated in infant baboons. MF59 consists of stable droplets (<250 nm) of the metabolizable oil squalene and two surfactants, polyoxyethylene sorbitan monooleate and sorbitan trioleate, in an oil-in-water emulsion. In humans, MF59 is well tolerated and enhances the immunogenicity of recombinant protein subunit or particle vaccines. Its effect on the immunogenicity of polysaccharide-protein conjugate vaccines is unknown. Baboons 1 to 4 months of age were immunized intramuscularly with Neisseria meningitidis group C and Haemophilus influenzae type b (Hib) oligosaccharide-CRM197 conjugate vaccines. The lyophilized vaccines were reconstituted with phosphate-buffered saline (PBS), Al(OH)3 (alum), or MF59. Groups of five animals each were given three injections of the respective formulations, with one injection every 4 weeks. Four weeks after each immunization, the MF59 group had up to 7-fold-higher geometric mean anticapsular-antibody titers than the alum group and 5- to 10-fold-higher N. meningitidis group C bactericidal-antibody titers. Twenty-one weeks after the third immunization, the MF59 group still showed 5- to 10-fold-higher anticapsular-antibody titers. The antibody responses of the animals given the vaccines reconstituted with PBS were low at all times measured. Both the MF59 and alum groups, but not the PBS group, showed booster antibody responses to unconjugated Hib and N. meningitidis group C polysaccharides, results consistent with induction of memory B cells. Thus, MF59 may be useful for accelerating and augmenting immunity to polysaccharide-protein conjugate vaccines in infants.     

Involvement of nitric oxide and cGMP in the protective effect of neurotensin on hepatocytes

STUDY OBJECTIVE: Tetanus antibody levels have been shown to be inadequate in 50% of patients older than 65 years. Although immunization recommendations have been made for this age group, the efficacy of this intervention has not been well documented. We sought to determine the difference in tetanus antibody levels after the administration of one tetanus toxoid immunization to geriatric patients without adequate titers. METHODS: Thirty-five patients older than 65 years at a large urban comprehensive care geriatric center who were documented to have inadequate tetanus antibody titers were each given one tetanus toxoid immunization. Repeat titers were obtained at least 2 months after the immunization with the use of enzyme-linked immunosorbent assay (Bindazyme kit; the Binding Site Corporation, Birmingham, England). We considered tetanus antibody levels greater than .17 IU/mL protective. RESULTS: The mean age was 79.4 years; 30 of 35 (86%) were female. Repeat tetanus antibody titers were obtained an average of 123 days (range, 63 to 204 days) after immunization with tetanus toxoid. The mean preimmunization antibody titer was .1 IU/mL (range, .04 to .16 IU/mL). After immunization, antibody titers increased a mean of .61 IU/mL (range, -.01 to 2.23 IU/mL; 95% confidence interval, .35 to .87 IU/mL). Thirty of the 35 patients who received a single injection of tetanus toxoid (86%) developed protective titers. We found no relationship between seroconversion and age, sex, or medical history; nor did we find a relationship between antibody level and time elapsed since immunization when repeat titers were obtained. CONCLUSION: Administration of one tetanus toxoid injection affords protective immunity in many geriatric patients.     

Maternal immunization against viral disease

The protective effect of maternal antibody against many viral diseases has been recognized. The use of maternal immunization has been considered as a means to augment this protection in the young infant against disease. Advantages of maternal immunization include the fact that young infants are most susceptible to infections but least responsive to vaccines, that pregnant women are accessible to medical care and respond well to vaccines, that IgG antibodies cross the placenta well during the third trimester, and that immunization of the pregnant woman has the potential to benefit both the mother and the infant. Disadvantages include the potential inhibition of an infant's response to active immunization or natural infection and liability issues with pharmaceutical companies and physicians. Immunization of pregnant women with viral vaccines for poliovirus, influenza viruses, and rubella has been described and maternal vaccination with these vaccines has been found to be safe for both the mother and the fetus. An open-label study of post-partum women immunized with the purified fusion protein of RSV (PFP-2, Wyeth-Lederle Pediatrics and Vaccines, Inc., Pearl River, NY) demonstrated that the vaccine was non-reactogenic and immunogenic; RSV-specific antibody was detected in breast milk. Immunization of pregnant women with purified protein or subunit vaccines could be considered against neonatal viral pathogens, such as respiratory syncytial virus, parainfluenza viruses, herpes group viruses, and human immunodeficiency virus. Further studies are needed to define the safety and efficacy of maternal immunization.