Persistence of protective anti-poliovirus antibody levels in 4-year-old children previously primed with Picovax®, a trivalent, aluminium-adjuvanted reduced dose inactivated polio vaccine
BackgroundTo meet the demand for effective and affordable inactivated polio vaccines (IPVs), a reduced dose, aluminium hydroxide (Al(OH)3)-adjuvanted IPV vaccine was developed (IPV-Al, Picovax®) and evaluated in clinical trials. The present trial is an extension of two previous trials (a primary and a booster trial). The aim was to evaluate the persistence of seroprotective antibodies (poliovirus type-specific antibody titre ≥ 8) in 4-year-old children who previously received IPV–Al as primary and booster vaccine doses and to determine the potential booster response and safety profile of an additional dose of IPV-Al. MethodsChildren participating in the two previous trials were invited to receive one additional dose of IPV-Al at 4 years of age (2.5 years after the booster dose) and to have their blood samples collected to measure the pre- and post-vaccination antibody titres. Systemic adverse events (AEs) and local reactogenicity were recorded. ResultsAt study entry, the seroprotection rates were 89.2%, 100% and 91.1% against poliovirus type 1, 2 and 3, respectively. The additional vaccination with IPV-Al boosted the level of poliovirus type 1, 2 and 3 antibodies to above the seroprotection threshold for all but one subject, i.e., 99.4% for type 1 and 100% for types 2 and 3. The additional dose induced a robust booster response of a 26.3-, 13.9- and 30.9-fold increase in titre for poliovirus types 1, 2 and 3, respectively. The vaccine was well tolerated, with only mild and transient AEs reported. ConclusionsThe present trial demonstrated that the primary vaccination with an aluminium-adjuvanted reduced dose IPV induced a persistent immune memory as evidenced by the robust anamnestic response when the subjects were re-exposed to the antigen 2.5 years after the last dose. Thus, the IPV-Al is an efficient and safe addition to increase the availability of inactivated polio vaccines globally. (ClinicalTrials.gov reg no. NCT04448132).
- Research Article
3
- 10.3760/cma.j.issn.0253-9624.2013.10.018
- Oct 1, 2013
- Chinese Journal of Preventive Medicine
To evaluate the immunogenicity and safety of a boost dose of inactivated polio vaccine (IPV) among children aged 18 months who had been administered with primary doses of IPV. Form 2011 to 2012, a total of 97 children were enrolled in the present study who were vaccinated with IPV at 2, 3, 4 months of age and boosted with the same vaccine at 18 months of age. Anti-poliovirus neutralizing antibody titers in serum were measured before and after booster vaccination, geometric mean titers (GMT) and seroprotection rate were calculated. Adverse events occurring within 30 days after booster vaccination were observed, including pain, redness/swelling and induration at the injection site, fever, vomit, abnormal crying, drowsiness, loss of appetite, irritability, and all other physical discomfort and related medications were also recorded. A descriptive analysis was performed for the safety assessment. Immunogenicity was assessed in 84 subjects. The pre-booster seropositivity rates of neutralizing antibody against poliovirus type 1, 2, 3 before booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 148.5 (116.49-189.29) , 1: 237.68 (178.39-316.67) and 1: 231.87 (181.27-296.58) , respectively. The seropositivity rates of neutralizing antibody against the three types of poliovirus after booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 1612.14 (1470.57-1767.34) , 1: 1854.92 (1715.83-2005.29) and 1: 1625.50 (1452.12-1819.58) , respectively. The pre-booster titer of neutralizing antibody against poliovirus type 1, 2, 3 mainly ranged 1: 128-1: 512, which accounted for 65% (55/84) , 55% (46/84) , 74% (62/84) in each type. After the booster immunization, titers of neutralizing antibody against type 1, 2, 3 were increased as subjects with titer ≥ 1: 1024 accounted for 94% (78/84) , 95% (80/84) , 92% (77/84) , respectively.Safety was evaluated in 96 subjects, of which 16 subjects reported adverse events with the rate of 17%. The observed local events were mainly tenderness 3% (3/96) , redness/swelling and induration were not reported. The systemic adverse events included loss of appetite (8%, 8/96) , irritability (8%, 8/96) , fever (7%, 7/96) , abnormal crying (6%, 6/96) , drowsiness (6%, 6/96) and vomit (1%, 1/96) . All reported adverse events were mild or moderate. All of the local events occurred in the day of vaccination and lasted for 1-2 days, while systemic events almost developed within 2 days after vaccination and last less than 3 days. IPV booster dose has good immunogenicity and safety profile, which provides effective protection against poliovirus.
- Research Article
39
- 10.4161/hv.2.6.3432
- Nov 1, 2006
- Human Vaccines
This study assessed the persistence of antibodies following primary vaccination with two commercially available, hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccines (Infanrix hexa™ and Hexavac™). The immunogenicity and reactogenicity of booster vaccination with Infanrix hexa™ were also evaluated. A total of 329 children primed at 2, 4, and 6 months with Infanrix hexa™ (n=166) or Hexavac™ (n=163) received booster vaccination with Infanrix hexa™ at 12-19 months of age. Antibody concentrations were measured immediately before and 1 month after booster vaccination. Pre-booster persistence of antibodies to HBs, PRP and poliovirus types was significantly higher in children primed with Infanrix hexa™ than with Hexavac™, both in terms of seroprotection rate and GMCs/GMTs (p < 0.05). Boosting with Infanrix hexa™ elicited strong immune responses to all antigens irrespective of the primary vaccine used, with post-booster seroprotection rates comparable between the two primary vaccine groups (ranging from 98.1 to 100%). The incidence of clinically relevant solicited symptoms did not differ significantly between primary vaccine groups, even if the incidence of local symptoms appeared to be more frequent in subjects primed with Infanrix hexa™ than in those primed with Hexavac™. In summary, booster vaccination with Infanrix hexa™ during the second year of life is immunogenic and well tolerated, offering protection irrespective of the primary combination vaccine used.
- Research Article
26
- 10.1186/1471-2334-14-142
- Mar 15, 2014
- BMC Infectious Diseases
BackgroundThe pandemic potential of avian influenza A/H5N1 should not be overlooked, and the continued development of vaccines against these highly pathogenic viruses is a public health priority.MethodsThis open-label extension booster study followed a Phase III study of 1206 adults who had received two 3.75 μg doses of primary AS03A-adjuvanted or non-adjuvanted H5N1 split-virus vaccine (A/Vietnam/1194/2004; clade 1) (NCT00449670). The aim of the extension study was to evaluate different timings for heterologous AS03A-adjuvanted booster vaccination (A/Indonesia/5/2005; clade 2.1) given at Month 6, 12, or 36 post-primary vaccination. Immunogenicity was assessed 21 days after each booster vaccination and the persistence of immune responses against the primary vaccine strain (A/Vietnam) and the booster strain (A/Indonesia) was evaluated up to Month 48 post-primary vaccination. Reactogenicity and safety were also assessed.ResultsAfter booster vaccination given at Month 6, HI antibody responses to primary vaccine, and booster vaccine strains were markedly higher with one dose of AS03A-H5N1 booster vaccine in the AS03A-adjuvanted primary vaccine group compared with two doses of booster vaccine in the non-adjuvanted primary vaccine group. HI antibody responses were robust against the primary and booster vaccine strains 21 days after boosting at Month 12 or 36. At Month 48, in subjects boosted at Month 6, 12, or 36, HI antibody titers of ≥1:40 against the booster strain persisted in 39.2%, 61.2%, and 95.6% of subjects, respectively. Neutralizing antibody responses and cell-mediated immune responses also showed that AS03A-H5N1 heterologous booster vaccination elicited robust immune responses within 21 days of boosting at Month 6, 12, or 36 post-primary vaccination. The booster vaccine was well tolerated, and no safety concerns were raised.ConclusionsIn Asian adults primed with two doses of AS03A-adjuvanted H5N1 pandemic influenza vaccine, strong cross-clade anamnestic antibody responses were observed after one dose of AS03A-H5N1 heterologous booster vaccine given at Month 6, 12, or 36 after priming, suggesting that AS03A-adjuvanted H5N1 vaccines may provide highly flexible prime–boost schedules. Although immunogenicity decreased with time, vaccinated populations could potentially be protected for up to three years after vaccination, which is likely to far exceed the peak of the a pandemic.
- Research Article
4
- 10.7196/samj.5022
- Nov 28, 2011
- South African Medical Journal
To assess the immunogenicity and safety of a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate vaccine booster. A DTaP-IPV//PRP~T vaccine (Pentaxim, a Sanofi Pasteur AcXim family vaccine) was given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent hepatitis B vaccine at 6, 10 and 14 weeks of age. Outcome measures. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titres (GMTs) and concentrations (GMCs) were assessed before, and 1 month after, the booster dose. Safety was assessed using parental reports. One month after primary vaccination, at least 94.3% of participants were seroprotected against tetanus (≥ 0.01 IU/ml), diphtheria (≥ 0.01 IU/ml), poliovirus (≥ 8 1/dil) and Haemophilus influenzae type b (Hib) infection (≥ 0.15 µg/ml). Before the booster dose, the SP rates ranged from 65.7% to 100%. One month after the booster dose, SP rates were 97.7% for Hib (anti-PRP titre 1.0 μg/ml), 100.0% for diphtheria (≥ 0.1 IU/ml) and 100% for tetanus (≥ 0.1 IU/ml) and poliovirus types 1, 2, 3 (≥ 8 1/dil). At least 95.7% of participants had 4 fold post-booster increases in anti-pertussis antibody titres. GMTs increased from 11.21 to 465.51 EU/ml and from 12.89 to 520.35 EU/ml for anti-PT and anti-FHA respectively. Anti-PRP GMT increased from 0.35 to 47.01 μg/ml. The DTaP-IPV//PRP~T vaccine booster was well tolerated, with fever ≥ 39.0°C in only 1.7% of participants. Antibody persistence following priming was satisfactory. The pentavalent DTaP-IPV//PRP~T vaccine booster was highly immunogenic and well tolerated.
- Research Article
39
- 10.1111/j.1708-8305.2006.00097.x
- Jan 1, 2007
- Journal of Travel Medicine
ecent cases of human rabies imported to Eu-rope by travelers visiting India and Morocco demonstrate the relevance and value of receiving proper education regarding rabies prevention, in-cluding both preexposure vaccination and postex-posure prophylaxis, prior to leaving for canine rabies – endemic countries. 1,2 This is especially rele-vant for travelers planning on visiting countries in Asia and Africa where the majority of human rabies cases occur. 3 Modern cell culture vaccines recommended by the World Health Organization (WHO), including purifi ed chick embryo cell vac-cine (PCECV), purifi ed Vero cell rabies vaccine, and human diploid cell rabies vaccine (HDCV), provide a safe means by which travelers can be pro-tected in the event of exposure to rabies virus. These vaccines have been licensed for several decades, but there are limited published data regarding the length of time after a person has received his or her primary rabies vaccination, for which they will continue to develop an anamnestic response after a booster dose of rabies vaccine has been adminis-tered. 4,5 The vaccination recommendations for a person who has been vaccinated previously with a cell culture rabies vaccine and is subsequently exposed to a rabid animal include the administra-tion of two booster doses of vaccine (one dose on day 0 and the other on day 3) without the adminis-tration of rabies immunoglobulin (RIG). However, the limited amount of available data has led to some confusion regarding booster recommendations in previously vaccinated persons who are subse-quently exposed to rabid animals. 6,7 To determine how long individuals would be able to mount an anamnestic response after primary vac-cination, we contacted all veterinarians who had ini-tially received PCECV as students enrolled in a clinical trial initiated in 1986. 8 The veterinarians who agreed to participate in this booster study veri-fi ed and confi rmed that they had not received a rabies booster vaccination for 14 years since the clin-ical trial was completed, and all agreed to provide their serum samples for serological evaluation before and after receiving a booster dose of rabies vaccine. In the initial clinical trial conducted in 1986, 78 individuals were vaccinated with either HDCV or PCECV intramuscularly or intradermally as a pri-mary three-dose series. 8 In 1988, 68 of the 78 subjects received a single 1.0 mL of PCECV in tramuscularly. After the booster dose in 1988, the mean titer for subjects who received intradermal dosage initially was 1,106 (range: 270 – 6,800) and for subjects who received intramuscular dosage for their initial series was 1,859 (range: 1,100 – 9,500). For comparison purposes, a reciprocal titer of 1:25 is approximately equal to a titer of 0.5 IU/mL. Fourteen years later, 15 of those who initially received PCECV and a dose of intramuscular booster 1 year after their primary se-ries and who had not received any additional rabies vaccination since the 1988 booster were enrolled in this study. After approval of the study by the ethics committee and obtaining informed consent from the subjects, a blood sample was obtained and a single
- Research Article
47
- 10.1016/j.vaccine.2016.09.058
- Oct 27, 2016
- Vaccine
Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans
- Research Article
23
- 10.1016/s0264-410x(99)00238-8
- Oct 11, 1999
- Vaccine
Studies on a Hib-tetanus toxoid conjugate vaccine: effects of co-administered tetanus toxoid vaccine, of administration route and of combined administration with an inactivated polio vaccine
- Research Article
92
- 10.1097/00007890-199703270-00008
- Mar 1, 1997
- Transplantation
Vaccination guidelines for transplant recipients include regular boosters of tetanus, diphtheria, and inactivated polio vaccine, but there are few published data on the efficacy of these vaccines in patients receiving immunosuppressive therapy. Serum antibody values were evaluated before and 4 weeks after tetanus, diphtheria, and inactivated polio vaccination in 164 renal transplant recipients compared with healthy controls. Twelve months later, antibody levels were evaluated in 55 patients. Prebooster tetanus antitoxin values were lower in transplant recipients than in controls. All patients developed protective tetanus antibody levels (> or = 0.01 IU/ml) after vaccination. After 12 months, serum antibodies had decreased, but all patients maintained protective values. Diphtheria antitoxin titers before and after booster vaccination were lower in patients than in controls: 88.5% of patients and 96.2% of controls developed protective diphtheria antibody values. Twelve months after vaccination, diphtheria antitoxin values were below the protective level (0.1 IU/ml) in 38% of patients. Prebooster antibody values to poliovirus types 1 and 3 were comparable in patients and controls, whereas antibodies to poliovirus type 2 were lower in transplant recipients. Seroprotection rates and geometric mean antibody titers after vaccination were equivalent between the two groups for all three poliovirus types. No difference was observed in antibody levels between patients on different immunosuppressive drug regimens. Adverse reactions were significantly less often reported by transplant recipients. In transplant recipients, tetanus and inactivated polio vaccinations are well tolerated and induce protective antibody levels; diphtheria vaccination as currently recommended is less effective and protective antitoxin values decrease rapidly in these patients within 1 year after vaccination.
- Research Article
36
- 10.1159/000046064
- Jan 1, 2001
- Nephron
Hepatitis B (HB) vaccine is effective in producing protection against HB virus infection, but the persistence of immunity remains largely unknown. Seventy-six hemodialysis (HD) patients (60 after primary HB vaccination and 16 with natural immunity) and 46 healthcare workers (32 after primary HB vaccination and 14 with natural immunity) were followed up for 10 years to evaluate the persistence of immunity. Ten years after vaccination, the analysis showed a lower seroconversion rate (38 vs. 75%, p < 0.001) in HD patients as compared with healthcare workers. In the follow-up period, the protective immunity developed through HB virus infection also showed a lower seroconversion rate (44 vs. 86%, p < 0.025) in HD patients as compared with healthcare workers. To assess the status of immunologic memory, we administered a booster dose of HB vaccine 3–12 years (mean 6.7 ± 0.6 years) after primary vaccination in a selected group of 37 HD patients who presented a decline of their antibodies or were nonresponders. In another group of 12 healthcare workers who had a decline of their antibodies, we also administered a booster dose of HB vaccine 5–8 years (mean 5.8 ± 0.3 years) after primary vaccination. Nineteen of the 37 HD patients (51%) presented an anamnestic response to the booster dose, and 15 of these (40%) were high responders. All of the healthcare workers responded to the booster dose with a high antibody response. We conclude that patients undergoing HD not only have lower rates of immunization to HB than healthy adults, but also that these are frequently transient. Booster doses after a primary course of vaccine are effective in about the half of HD patients who presented a decline of their antibodies or were nonresponders but whether they are necessary is unclear. The majority of healthcare workers continue to have high levels of protective HBs antibody for at least 10 years and routine boosters are not required.
- Research Article
- 10.3760/cma.j.issn.0254-6450.2017.05.013
- May 10, 2017
- Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
Objective: To evaluate the safety and immunogenicity of one booster dose of inactivated hepatitis A vaccine in young adults. Methods: The subjects were selected from participants in the clinical trial of immunogenicity of inactivated and attenuated live hepatitis A vaccine in young adults. Eligible subjects were those who had received one dose of inactivated or attenuated hepatitis A vaccine, could be contacted and were sero-negative before primary vaccination. All qualified subjects were immunized with one booster dose of inactivated hepatitis A vaccine. The blood samples were collected before booster dose vaccination and 28 days after the immunization. Anti-HAV antibody titer ≥20 mIU/ml was considered to be sero-protected against hepatitis A virus. Results: The GMCs in the inactivated HAV vaccine group and attenuated live vaccine group before booster dose vaccination were 70.80 mIU/ml and 50.12 mIU/ml, respectively, and the sero-protection rates were 94.7% and 65.0%, respectively. After the vaccination of the booster dose, the sero-protection rates in both groups were 100.0%, and the GMCs were 2 816.09 mIU/ml and 2 654.55 mIU/ml, respectively. Conclusion: The GMCs and sero-protection rates of anti-HAV antibody in young adults declined after three years of the primary vaccination. However, the higher GMC and sero-protection rate were observed in the inactivated vaccine group than in the attenuated live vaccine group. Significant increases of GMC levels were observed in both groups after one booster dose vaccination.
- Research Article
41
- 10.1097/inf.0000000000001601
- Dec 1, 2017
- Pediatric Infectious Disease Journal
Maternal immunization with a tetanus, diphtheria and acellular pertussis (Tdap) vaccine may blunt infant pneumococcal immune responses after a primary series of vaccines. As part of a prospective controlled cohort trial of Tdap (Boostrix; GSK Biologicals, Rixensart, Belgium) vaccination in pregnancy, infants born to vaccinated mothers and controls were immunized at 8 and 16 weeks and 12 months of age with 13-valent pneumococcal conjugate vaccine (Prevenar13; Pfizer, Wyeth, United States). Sera were tested for pneumococcal antibody concentrations against vaccine serotypes following primary and booster immunization. Geometric mean concentration of antibodies to serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14 and 19A was significantly lower after 2 doses of Prevenar13 vaccine in the offspring of the mothers vaccinated in pregnancy. This blunting effect disappeared after a booster dose at 12 months of age, except for serotypes 1 and 4. Despite this blunting, the percentage of children achieving the threshold of protection of 0.35 µg/mL was comparable in the vaccine and the control group both after primary and booster vaccination with only a significant lower rate of seroprotection in the vaccine group for serotype 3 after primary vaccination. After booster vaccination, seroprotection rates increased further for serotypes 3, 5, 6B, 9V and 23F. The present results indicate a blunting effect after primary vaccination for some serotypes resolving after booster vaccination. Seroprotection rates were comparable both after primary and booster vaccination, except for serotype 3 with a significant lower seroprotection rate in the vaccine group after primary vaccination.
- Research Article
12
- 10.1016/j.vaccine.2020.02.066
- Apr 6, 2020
- Vaccine
BackgroundAvailability of affordable inactivated polio vaccines (IPV) is of major importance to meet the increasing global supply needs. The results presented here demonstrate non-inferiority of a reduced-dose, aluminium hydroxide-adjuvanted IPV (IPV-Al) to standard IPV. MethodsA phase 3, observer-blinded, randomised, clinical trial was conducted in Panama in infants who received either IPV-Al (n = 400) or standard IPV (n = 400) at age 2, 4 and 6 months. In the booster trial, subjects received a single dose of IPV-Al at age 15–18 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series. In the booster trial, the primary endpoint was the type-specific booster effects (geometric mean titre (GMT) post-booster (Day 28)/GMT pre-booster (Day 0). ResultsSeroconversion rates following primary vaccination with IPV-Al vs IPV were: 96.1% vs 100% (type 1); 100% vs 100% (type 2); and 99.2% vs 100% (type 3) respectively. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the pre-defined −10%-point limit: 3.94% (-6.51; −2.01) for type 1; 0.0% (-1.30; −1.37) for type 2; −0.85 (-2.46; 0.40) for type 3. The booster effects for the group primed with IPV-Al versus the group primed with IPV were 25.3 vs 9.2 (type 1), 19.1 vs 6.5 (type 2) and 50.4 vs 12.5 (type 3). IPV-Al had a comparable safety profile to that of IPV. ConclusionsNon-inferiority of IPV-Al to standard IPV with respect to seroconversion after vaccination at 2, 4 and 6 months was confirmed for all three poliovirus serotypes. A robust booster response was demonstrated following vaccination with IPV-Al, regardless of the primary vaccine received. Both vaccines were well tolerated.ClinicalTrials.gov identifiers: NCT03025750 and NCT03671616.Funding: Bill & Melinda Gates Foundation.
- Research Article
7
- 10.3389/fimmu.2022.990071
- Sep 20, 2022
- Frontiers in Immunology
Although immune response enhancement has been reported after primary and booster vaccines of CoronaVac, neutralization breadth of SARS-CoV-2 variants is still unclear. In the present study, we examined the neutralization magnitude and breadth of SARS-CoV-2 variants including Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) in 33 convalescent COVID-19 patients and a cohort of 55 medical staff receiving primary CoronaVac vaccines and an additional homologous booster dose. Results showed that, as compared with the two-dose primary vaccination, the homologous booster dose achieved 2.24-, 3.98-, 4.58- and 2.90-fold increase in neutralization titer against wild-type, Beta, Delta, and Omicron, respectively. After booster dose, neutralization titer reduction for variants was less than that after the primary vaccine or that for convalescents. The proportion of recipients able to neutralize 2 or more variants increased from 36.36% post the primary vaccination to 87.27% after the booster. Significant increase in neutralization breadth of 1.24 (95% confidence interval (CI), 0.89–1.59) variants was associated with a log10 increase in neutralization titer against the wild-type. In addition, anti-RBD IgG level was identified as an excellent surrogate for positive neutralization of SARS-CoV-2 and neutralization breadth of variants. These findings highlight the value of an additional homologous CoronaVac dose in broadening the cross-neutralization against SARS-CoV-2 variants, and are critical for informing the booster dose vaccination efforts.
- Research Article
17
- 10.1016/s1473-3099(17)30177-9
- Apr 25, 2017
- The Lancet. Infectious Diseases
SummaryBackgroundCost and supply constraints are key challenges in the use of inactivated polio vaccine (IPV). Dose reduction through adsorption to aluminium hydroxide (Al) is a promising option, and establishing its effectiveness in the target population is a crucial milestone in developing IPV-Al. The aim of this clinical trial was to show the non-inferiority of three IPV-Al vaccines to standard IPV.MethodsIn this phase 2, non-inferiority, observer-blinded, randomised, controlled, single-centre trial in the Dominican Republic, healthy infants aged 6 weeks, not previously polio vaccinated, were allocated after computer-generated randomisation by block-size of four, to receive one of four IPV formulations (three-times reduced dose [1/3 IPV-Al], five-times reduced dose [1/5 IPV-Al], ten-times reduced dose [1/10 IPV-Al], or IPV) intramuscularly in the thigh at 6, 10, and 14 weeks of age. The primary outcome was seroconversion for poliovirus types 1, 2, and 3 with titres more than or equal to four-fold higher than the estimated maternal antibody titre and more than or equal to 8 after three vaccinations. Non-inferiority was concluded if the lower two-sided 90% CI of the seroconversion rate difference between IPV-Al and IPV was greater than −10%. The safety analyses were based on the safety analysis set (randomly assigned participants who received at least one trial vaccination) and the immunogenicity analyses were based on the per-protocol population. This study is registered with ClinicalTrials.gov registration, number NCT02347423.FindingsBetween Feb 2, 2015, and Sept 26, 2015, we recruited 824 infants. The per-protocol population included 820 infants; 205 were randomly assigned to receive 1/3 IPV-Al, 205 to receive 1/5 IPV-Al, 204 to receive 1/10 IPV-Al, and 206 to receive IPV. The proportion of individuals meeting the primary endpoint of seroconversion for poliovirus types 1, 2, and 3 was already high for the three IPV-Al vaccines after two vaccinations, but was higher after three vaccinations (ie, after completion of the expanded programme of immunisation schedule): 1/3 IPV-Al 98·5% (n=202, type 1), 97·6% (n=200; type 2), and 99·5% (n=204, type 3); 1/5 IPV-Al: 99·5% (n=204, type 1), 96·1% (n=197, type 2), and 98·5% (n=202, type 3); and 1/10 IPV-Al: 98·5% (n=201, type 1), 94·6% (n=193, type 2), and 99·5% (n=203, type 3). All three IPV-Al were non-inferior to IPV, with absolute differences in percentage seroconversion for each poliovirus type being greater than −10% (1/3 IPV-Al type 1, −1·46 [–3·60 to 0·10], type 2, −0·98 [–3·62 to 1·49], and type 3, −0·49 [–2·16 to 0·86]; 1/5 IPV-Al type 1, −0·49 [–2·16 to 0·86], type 2, −2·45 [–5·47 to 0·27], and type 3, −1·46 [–3·60 to 0·10]; and 1/10 IPV-Al type 1, −1·47 [–3·62 to 0·10], type 2, −3·94 [–7·28 to −0·97], and type 3, −0·49 [–2·17 to 0·86]). Three serious adverse events occurred that were unrelated to the vaccine.InterpretationThe lowest dose (1/10 IPV-Al) of the vaccine performed well both after two and three doses. Based on these results, this new vaccine is under investigation in phase 3 trials.FundingBill & Melinda Gates Foundation.
- Research Article
7
- 10.1186/1471-2334-10-347
- Dec 1, 2010
- BMC Infectious Diseases
BackgroundIn October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster.MethodsNeutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines.ResultsThe neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P < 0.025). In eight sera, the antibody titres measured against CHAT were less than 8, although the titre against Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally.ConclusionThe lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We strongly suggest that laboratory workers who were immunised with OPV receive a booster vaccination with IPV before handling CHAT in the laboratory.