Immunization of healthy children with measles-mumps-rubella trivalent vaccine simultaneously given with varicella vaccine]

Trivalent vaccine, containing measles TD97, rubella TCRB-19 and mumps NK-M46 strains (MMR vaccine) was administered to a total of 116 healthy children of which 50 subjects were simultaneously injected with varicella vaccine in the opposite arm. The seroconversion rates for measles, mumps, rubella, and varicella in those who received both MMR and varicella vaccines (MMR + V group) were 100% (44/44), 91% (39/43), 100% (46/46) and 95% (39/41), respectively. And these rates were comparable to those in subjects receiving only MMR vaccine, namely 100% (64/64) for measles, 95% (57/62) for mumps, and 97% (58/60) for rubella. Fifty-eight children receiving MMR vaccine were seronegative to measles, mumps and rubella before vaccination, and 51 (88%) of them were found to be seropositive against all three viruses at 6 to 8 weeks after vaccination. Among the children injected with MMR and varicella vaccines, 36 subjects had no pre-antibodies to measles, mumps, rubella and varicella. Seroconversion in post-serum to all four viruses were found in 31 cases (86%). Clinical reactions observed in some vaccines were mild fever (17%) and exanthem (5%). There were no complications of lymphadenopathy, swelling in parotid regions, or meningitis. Our results indicate that simultaneous administration of MMR vaccine and varicella vaccine is a safe and effective method for immunizing children against these four infectious diseases.     

Cell-mediated immune responses after immunization of healthy seronegative children with varicella vaccine: kinetics and specificity

Humoral and cell-mediated immune responses were determined in seronegative children immunized with live attenuated Oka strain varicella vaccine. At 2 weeks after immunization, 80% of children had detectable lymphocyte proliferation to varicella-zoster virus (VZV) antigens, while only 40% had antibodies to VZV as detected by ELISA. By 6 weeks after immunization, 97% of children seroconverted, and 95% of these responded to VZV antigens in the proliferation assay. A high proportion of immunized children also responded in the proliferation assay to purified glycoproteins I, II, and III of VZV. These results indicate that most children develop a broad cell-mediated immune response to VZV antigens within weeks after immunization with varicella vaccine.     

Humoral and cell-mediated immune responses in children and adults after 1 and 2 doses of varicella vaccine

Humoral and cell-mediated immune responses to varicella-zoster virus (VZV) have been evaluated after 1 and 2 doses of live attenuated varicella vaccine, Oka strain, in several studies. One dose of varicella vaccine, however, elicits detectable immune responses that are low and, in some cases, may be insufficient for complete protection against the virus after the normal decline in humoral and cell-mediated immunity with time. In contrast, immune responses after 2 doses are significantly higher and approximate the levels seen after natural disease. These investigations of vaccine-induced immunity suggest that 2 doses of VZV vaccine will better achieve the goals of the VZV vaccination program, by reducing the VZV burden of disease in childhood and preventing accumulation of young adults who are susceptible to or only partially protected from varicella.     

Immunization of healthy adults with live attenuated varicella vaccine

Live attenuated varicella vaccine was administered to healthy varicella-susceptible adults. Of 187 adults immunized with the Oka strain of vaccine, seroconversion to varicella-zoster virus (VZV) occurred in 82% after one dose and in 94% after two doses. Adverse effects were unusual. After immunization, one subject developed mild zoster caused by wild-type virus. Twelve adults developed a mild breakthrough case of chickenpox after exposure to VZV. Protection after household exposure was observed in nine (56%) of 16; however, the illness in all seven patients with breakthrough illness was modified, with an average of only 24 vesicles. Subjects seropositive at household exposure were unlikely to develop a breakthrough illness. Approximately 25% of vaccinees who seroconverted lost detectable antibodies to VZV after vaccination, but even those who became seronegative were partially protected. Varicella vaccine offered significant protection against severe chickenpox in healthy adults.     

Mild varicella observed in children vaccinated with varicella vaccine between 1984 and 1987

We investigated varicella cases developed in children who received varicella vaccine in the period from October 1984 to March 1987. In this period 463 children were vaccinated and 334 of the vaccines were seronegative before injection. Seroconversion was observed in 276 seronegative vaccinees producing a seroconversion rate of 83.1%. Thirty-five children developed exanthem more than 4 weeks after the vaccination and were diagnosed as varicella. Among them one child was found to be antibody-positive in his preserum and five were seronegative in both their pre- and post-sera. Thus, among the children who were seroconverted by the vaccination only 30 had varicella (the attack rate = 10.9%). No varicella cases were reported, however, among 27 children who first became seropositive after revaccination. When these children were added to the seroconverted ones, the case rate amounted to 9.9% (30/303). The general symptoms of varicella observed in the vaccinated children were mild or extremely mild, so varicella vaccine is reasonably indicated to be efficient and useful although it could no completely protect the vaccinees from natural varicella.     

Reactogenicity to a live attenuated varicella vaccine in Canadian children

OBJECTIVE:

To assess the reactogenicity and safety of a thermostable, high titre, varicella vaccine in healthy infants and children.

DESIGN:

Open study of 505 children monitored for 42 days after vaccination.

SETTING:

Three urban Canadian centres (Halifax, Ottawa and Vancouver).

PARTICIPANTS:

505 healthy children one to 12 years of age were enrolled and 504 completed the study. All were susceptible to varicella by history.

INTERVENTIONS:

All participants received one dose of live attenuated varicella vaccine (1x10^4.5 plaque forming units/dose) subcutaneously.

MAIN OUTCOME MEASURES:

The children were monitored from the day of vaccine administration (day 0) until day 42. All local and general symptoms and signs were recorded on diary cards by the patients'' parents, who were encouraged to fill in the cards on days 2 to 3 and 18 to 24 via telephone calls from study personnel.

RESULTS:

Most of the symptoms noted after vaccine administration were mild and transient, and all resolved within the respective follow-up periods. Injection site symptoms included pain (17.5%, 13.9% and 30.4% in centres 1, 2 and 3 respectively), redness (21.1%, 32.1% and 48.8%) and swelling (7%, 10.3% and 29.2%). The general symptoms reported were fever 37.5°C or higher (3.5%, 4.8% and 3.0%) and varicella-like rashes (6.4%, 2.4% and 0%). Two subjects had severe symptoms (one with cervical lymphadenopathy, and one with a fever higher than 39°C) probably related to vaccine administration. No serious adverse events were reported during the entire study.

CONCLUSION:

The vaccine was well tolerated.Key Words: Chickenpox, Reactogenicity, Varicella vaccineInfection by varicella zoster virus (VZV) usually results in benign disease in children. However, complications such as pneumonia, encephalitis and bacterial superinfection of the skin lesions (1,2) occur in some patients, mainly in adolescents and adults, and in immunocompromised children (1,2). In addition, children born to nonimmune mothers who contract varicella during pregnancy can develop congenital varicella syndrome (1,3), with limb hypoplasia and central nervous system damage.A live varicella vaccine was developed in Japan in 1974 (4) using the OKA strain of the virus. The original wild type virus was isolated from a boy with natural varicella, and then attenuated by passages through human and guinea pig embryonic cells, and two human diploid cell lines, WI-38 and MRC-5 (4,5). The vaccine strain obtained after this treatment has different thermosensitivity and host range spectrum than the wild type virus (6). Additionally, it can be easily differentiated from wild type strains currently circulating in North America by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) testing (6,7).All OKA varicella vaccine production lots are derived directly from a working seed lot (8), following the World Health Organization guidelines (9). Many clinical trials have demonstrated that this strain is safe and immunogenic (2,5,10,11). The vaccine produced by SmithKline Beecham Biologicals (Rixensart, Belgium), VARILRIX, was first licensed in Europe in 1984 (10,11). An OKA-strain varicella vaccine, Oka/Biken (Biken, Osaka, Japan), has been licensed in Japan since 1987 (5). Vaccines using the same strain, were licensed in the United States in 1995 (Oka/Merck or VARIVAX, Merck and Company Inc, Whitehouse Station, New Jersey [12]) and in France in 1997 (Pasteur Merieux, Lyon, France).SmithKline Beecham Biologicals introduced recently a reformulation of the vaccine to increase its stability at 2 to 8°C and, therefore, facilitate its use for general vaccination (10). The vaccine will retain a titre of 1x10^3.3 plaque forming units (PFU) or more/dose after two years at 2 to 8°C. The safety and immunogenicity of this vaccine have been extensively tested (10,11).We conducted a multicentre study to assess the reactogenicity and safety of two lots of the reformulated varicella zoster vaccine produced by SmithKline Beecham Biologicals in children from one to 12 years of age. This vaccine has a higher titre (approximately 1x10^4.5 PFU per dose) of virus at release and is more thermostable than the vaccine presently licensed in Canada. The purpose of the study was to obtain daily information on local and general reactogenicity to the vaccine. Such information is required by licensing agencies before a vaccine is made available to the public.     

Reactogenicity and immunogenicity of a varicella vaccine in healthy seronegative and seropositive subjects

The epidemiology of varicella appears to be changing: an unexplained upward age shift in varicella prevalence and a subsequent dramatic rise in morbidity and mortality among adolescents and adults have highlighted the importance of effective varicella mass vaccination programs. This age shift is being seen in temperate regions but is particularly marked in tropical and sub-tropical regions. To assess the need for serological pre-screening in mass vaccination programs, we performed an open study to compare the reactogenicity and immunogenicity of a varicella vaccine in initially seronegative and seropositive subjects to see whether there was an increase in reactogenicity among initially seropositive subjects. Two hundred and forty-six seronegative and seropositive male and female subjects, aged 9 months to 60 years, received a single dose of a live attenuated varicella virus (Oka-strain) vaccine, Varilrix (GlaxoSmithKline Biologicals, Rixensart, Belgium). Subjects were categorized according to antibody status and age group; serum antibodies were measured before and after vaccination (day 42). The study showed that there was no difference in reactogenicity in initially seropositive vaccinees compared with initially seronegative subjects. The varicella vaccine was found to be safe and well tolerated in all age groups. Ninety-eight percent of initially seropositive and 94.8% of initially seronegative subjects reported no clinical signs or symptoms during the 42-day follow-up period. The vaccine was immunogenic in both groups. The seroconversion rate after 6 weeks in initially seronegative subjects was 94.3%. In 53.0% of initially seropositive subjects of all age classes, a 4-fold rise in antibody titer was observed.     

Immunization of healthy children with mumps-rubella bivalent live vaccine and simultaneous vaccination with mumps-rubella and varicella vaccines]

Bivalent virus vaccine, containing rubella TCRB-19 strain and mumps NK-M46 strain (MR vaccine), was administered to a total of 95 healthy children who had already received measles vaccine or had been infected with wild measles virus. The seroconversion rates for rubella and mumps viruses in subjects having no antibody to rubella or to mumps virus were 99% (75/76) and 97% (63/65), respectively, at 6-8 weeks after vaccination. The seroconversion rates for both rubella and mumps in vaccinees initially seronegative to both viruses were 95% (56/59). Immune responses after MR vaccine injection were comparable to those after administration of monovalent rubella or mumps vaccine. Clinical reactions observed in some subjects who received MR vaccine were mild fever (3.6%), exanthem (8%), lymphadenopathy (1.8%), and swelling of the parotis region (1.8%). MR vaccine could be simultaneously injected with varicella vaccine at the opposite site producing no adverse effect on immune response. Our results indicate that MR vaccine is a safe and effective vaccine, especially for children who have had wild measles or who have received measles vaccine.     

Younger age at vaccination may increase risk of varicella vaccine failure

To determine vaccine effectiveness (VE), a varicella outbreak in a highly vaccinated day-care center (DCC) population in Pennsylvania was investigated. In Pennsylvania, proof of immunity is required for children >or=12 months old for DCC enrollment. Questionnaires were administered to parents of children who had attended the DCC continuously during the study period (1 November 1999-9 April 2000) to determine history of varicella disease or vaccination and for information about any recent rash illnesses. VE was calculated for children >or=12 months old without a history of varicella. There were 41 cases of varicella among 131 attendees, with 14 cases (34%) among vaccinated children. VE was 79% against all varicella and 95% against moderate or severe varicella. Vaccination at <14 months was associated with an increased risk of breakthrough disease (relative risk, 3.0; 95% confidence interval, 0.9-9.9). Despite varicella vaccination coverage of 80%, a sizeable outbreak occurred. Early age at vaccination may increase the risk of vaccine failure.     

Reactogenicity to a live attenuated varicella vaccine in Canadian children.

OBJECTIVE: To assess the reactogenicity and safety of a thermostable, high titre, varicella vaccine in healthy infants and children. DESIGN: Open study of 505 children monitored for 42 days after vaccination. SETTING: Three urban Canadian centres (Halifax, Ottawa and Vancouver). PARTICIPANTS: 505 healthy children one to 12 years of age were enrolled and 504 completed the study. All were susceptible to varicella by history. INTERVENTIONS: All participants received one dose of live attenuated varicella vaccine (1x10(4.5) plaque forming units/dose) subcutaneously. MAIN OUTCOME MEASURES: The children were monitored from the day of vaccine administration (day 0) until day 42. All local and general symptoms and signs were recorded on diary cards by the patients' parents, who were encouraged to fill in the cards on days 2 to 3 and 18 to 24 via telephone calls from study personnel. RESULTS: Most of the symptoms noted after vaccine administration were mild and transient, and all resolved within the respective follow-up periods. Injection site symptoms included pain (17.5%, 13.9% and 30.4% in centres 1, 2 and 3 respectively), redness (21.1%, 32.1% and 48.8%) and swelling (7%, 10.3% and 29.2%). The general symptoms reported were fever 37.5 degrees C or higher (3.5%, 4.8% and 3.0%) and varicella-like rashes (6.4%, 2.4% and 0%). Two subjects had severe symptoms (one with cervical lymphadenopathy, and one with a fever higher than 39 degrees C) probably related to vaccine administration. No serious adverse events were reported during the entire study. CONCLUSION: The vaccine was well tolerated.     

Immunogenicity of a two-dose regime of varicella vaccine in children with cancers

OBJECTIVE: Live-attenuated varicella vaccine is effective and safe in immunocompetent children. In this study, we assess the immunogenicity and adverse events following varicella vaccination in immunosuppressed cancer children. METHODS: Varicella-zoster virus (VZV)-seronegative cancer children received two doses of live-attenuated VZV vaccine (Varilrix) in a span of 3 months. Patients with acute lymphoblastic leukaemia (ALL) were in the maintenance phase of chemotherapy, whereas those with solid tumours joined the study around 3-6 months from treatment discontinuation. VZV-specific cellular and humoral immune responses were measured before and after VZV vaccination. RESULTS: The median (range) age of the 17 patients was 4.4 yr (2.0-14.5). Thirteen had ALL, one had myelodysplastic syndrome and three had solid tumours. Following vaccination, the VZV-specific stimulation index (SI) increased from 1.7 (0.9-2.9) to 17.9 (5.9-36.0) (P < 0.001). Similarly, SI to phytohaemagglutinin mitogen increased from 1136 (499-1930) to 1714 (848-2518) (P = 0.028). There were also significant increases in CD4+ cells and CD4:CD8 ratio as well as a reduction in CD16/56+ cells in peripheral blood lymphocytes. Seroconversion rate to VZV was 19% after one dose and increased to 94% after the second dose of VZV vaccine. Serum VZV-specific IgG concentrations also increased significantly following two doses when compared with one dose of VZV vaccine (P = 0.0004). One subject developed possibly vaccine-related chickenpox with self-limiting hepatitis at 5 wk following vaccination. None of the patients developed herpes-zoster at a median (range) follow-up of 27.5 months (24.0-30.0). CONCLUSIONS: Non-immune cancer children can be effectively vaccinated against chickenpox at the defined period. However, the safety of chickenpox vaccine in these immunosuppressed children needs to be further studied.     

Development of varicella vaccine

The Oka strain of varicella-zoster virus (VZV) was first isolated from vesicles of an otherwise healthy 3-year-old boy with typical varicella. The virus was passaged 11 times in human embryonic lung fibroblasts at 34 degrees C and 12 times in guinea pig embryo fibroblasts (GPEFs) at 37 degrees C. GPEFs were the only nonprimate cells tested in which some degree of viral replication occurred. The resultant virus was temperature sensitive and showed host dependency, measured as better replication in GPEFs than that shown by the parental virus. The passaged virus was used as a candidate varicella vaccine and proved safe and effective for healthy and immunocompromised children. During the follow-up of vaccinated children with acute lymphocytic leukemia, the incidence of herpes zoster (HZ) was significantly lower among children who did not have a rash after vaccination, compared with those who had a rash caused by VZV (6 [2.3%] of 260 vs. 12 [17.1%] of 70, respectively). Because of the pathogenesis of VZV, the incidence of latency and of HZ is predicted to be lower among vaccine recipients than among individuals who have experienced varicella.     

Advantage of a two-dose versus one-dose varicella vaccine in healthy non-immune teenagers and young adults

This study was undertaken to compare the immunogenicity and reactogenicity of two vaccines based on the attenuated Oka-strain of Varicella zoster virus (VZV), in adolescents and young adults. One hundred and eighty-six subjects, aged 13 to 29 years, were randomized to one of two groups to receive a one- or a two-dose VZV vaccine. Pre- and post-vaccination blood samples were assayed for VZV-specific IgG. Solicited local and general symptoms, as well as unsolicited symptoms, were recorded post-vaccination. Seroconversion rates were 94.9% in the one-dose, and 100% in the two-dose, regimen. The two-dose vaccine elicited significantly higher geometric mean antibody titer, 392.5 vs 86.8 pfu. Transient local injection site pain was the most frequently-reported symptom per dose in both groups (one dose: 48.9%; two-dose: 32.8%). The two-dose vaccine regimen afforded the advantage of higher antibody titers and potential increased protection from disease, without significantly increased reactogenicity.     

An elementary school outbreak of varicella attributed to vaccine failure: policy implications

BACKGROUND: Since licensure in the United States, studies have shown that varicella vaccine's overall effectiveness ranges from 44% to 100%, with substantial protection against moderate and severe varicella; however, breakthrough illness has been documented in up to 56% of vaccinated individuals. METHODS: A varicella outbreak occurred in a Minnesota school with 319 students. Phone surveys were conducted with students' parents. Information was collected on students who had recent varicella infections, including onset date, rash characteristics, duration, and underlying medical conditions. RESULTS: Fifty-four cases occurred after a primary breakthrough case. Twenty-nine (53%) students had been vaccinated. Unvaccinated students had an increased risk of moderate varicella, compared with vaccinated students (relative risk [RR], 4.4 [95% confidence interval [CI], 2.2-9.1]; P<.001). The vaccine was 56% effective at preventing any varicella and 90% effective against moderate illness. Students vaccinated >or=5 years before the outbreak had a greater risk of breakthrough varicella than did those vaccinated within 相似文献