Early smallpox vaccine manufacturing in the United States: Introduction of the “animal vaccine” in 1870, establishment of “vaccine farms”, and the beginnings of the vaccine industry

For the first 80–90 years after Jenner’s discovery of vaccination in 1796, the main strategy used to disseminate and maintain the smallpox vaccine was arm-to-arm vaccination, also known as Jennerian or humanized vaccination. A major advance occurred after 1860 with the development of what was known as “animal vaccine”, which referred to growing vaccine material from serial propagation in calves before use in humans. The use of “animal vaccine” had several advantages over arm-to-arm vaccination: it would not transmit syphilis or other human diseases, it ensured a supply of vaccine even in the absence of the spontaneous occurrence of cases of cowpox or horsepox, and it allowed the production of large amounts of vaccine. The “animal vaccine” concept was introduced in the United States in 1870 by Henry Austin Martin. Very rapidly a number of “vaccine farms” were established in the U.S. and produced large quantities of “animal vaccine”. These “vaccine farms” were mostly established by medical doctors who saw an opportunity to respond to an increasing demand of smallpox vaccine from individuals and from health authorities, and to make a profit. The “vaccine farms” evolved from producing only smallpox “animal vaccine” to manufacturing several other biologics, including diphtheria- and other antitoxins. Two major incidents of tetanus contamination happened in 1901, which led to the promulgation of the Biologics Control Act of 1902. The US Secretary of the Treasury issued licenses to produce and sell biologicals, mainly vaccines and antitoxins. Through several mergers and acquisitions, the initial biologics licensees eventually evolved into some of the current major American industrial vaccine companies. An important aspect that was never clarified was the source of the vaccine stocks used to manufacture the smallpox “animal vaccines”. Most likely, different smallpox vaccine stocks were repeatedly introduced from Europe, resulting in polyclonal vaccines that are now recognized as “variants” more appropriately than “strains”. Further, clonal analysis of modern “animal vaccines” indicate that they are probably derived from complex recombinational events between different strains of vaccinia and horsepox. Modern sequencing technologies are now been used by us to study old smallpox vaccine specimens in an effort to better understand the origin and evolution of the vaccines that were used to eradicate the smallpox.     

Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age

Background

Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV.

Methods

Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card.

Results

No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10⁶ peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor.

Conclusions

ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.     

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013–18

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses.MethodsVE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed.ResultsIn the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505–0.621], 0.550 [95% CI, 0.516–0.586]), 0.549 [95% CI, 0.517–0.583], and 1.014 [95% CI, 0.907–1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1–12 years, especially among those aged 1–5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A.ConclusionsBoth one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.     

Comparison of vaccine effectiveness against influenza hospitalization of cell-based and egg-based influenza vaccines, 2017–2018

Egg-based influenza vaccines could be less effective than cell-based vaccine due to adaptive mutations acquired for growth. We conducted a test-negative case-control study at Kaiser Permanente Southern California to assess vaccine effectiveness (VE) against hospitalization for laboratory-confirmed influenza during 2017–2018. Among the 1186 cases and 6946 controls, 74% and 59%, respectively, were ages ≥ 65 years. For any influenza, the adjusted relative VE of cell-based vaccine versus egg-based vaccines was 43% (95% CI: −45% to 77%) for patients ages < 65 years and 6% (95% CI: −46% to 39%) for patients ages ≥ 65 years. For influenza A(H3N2), the adjusted relative VE was 61% (95% CI: −63% to 91%) for patients ages < 65 years and −4% (95% CI: −70% to 37%) for patients ages ≥ 65 years. Statistically significant protection against influenza hospitalization of cell-based vaccine compared to egg-based vaccines was not observed, but further studies in additional influenza seasons are warranted.     

Social norms and vaccine uptake: College students’ COVID vaccination intentions,attitudes, and estimated peer norms and comparisons with influenza vaccine

BackgroundVaccination may be critical to curtailing the spread of the SARS-CoV-2 virus responsible for the COVID-19 pandemic, but herd immunity can only be realized with high vaccination coverage. There is a need to identify empirically supported strategies to increase uptake, especially among young adults as this subpopulation has shown relatively poor adherence to physical distancing guidelines. Social norms – estimates of peers’ behavior and attitudes – are robust predictors of health behaviors and norms-based intervention strategies may increase COVID vaccine uptake, once available. This study examined the extent that vaccination intentions and attitudes were associated with estimated social norms as an initial proof-of-concept test.MethodIn November of 2020, 647 undergraduate students (46.21% response rate) completed online surveys in which they reported intentions to get COVID and influenza vaccines, perceived importance of these vaccines for young adults, and estimated social norms regarding peers’ vaccination behaviors and attitudes.ResultsStudents reported significantly greater intentions to get a COVID vaccine (91.64%) than an influenza vaccine (76.04%), and perceived COVID vaccination as significantly more important than influenza vaccination. The sample generally held strong intentions to receive a COVID vaccine and thought that doing so was of high importance, but participants, on average, perceived that other young adults would be less likely to be vaccinated and would not think vaccination was as important. Multiple regression models indicated that estimated social norms were positively associated with participants’ own intentions and perceived importance of getting a COVID vaccine.ConclusionsThese significant associations highlight the potential value in developing and testing norms-based intervention strategies, such as personalized normative feedback, to improve uptake of forthcoming COVID vaccines among young adults.     

The complexity and cost of vaccine manufacturing – An overview

As companies, countries, and governments consider investments in vaccine production for routine immunization and outbreak response, understanding the complexity and cost drivers associated with vaccine production will help to inform business decisions. Leading multinational corporations have good understanding of the complex manufacturing processes, high technological and R&D barriers to entry, and the costs associated with vaccine production. However, decision makers in developing countries, donors and investors may not be aware of the factors that continue to limit the number of new manufacturers and have caused attrition and consolidation among existing manufacturers. This paper describes the processes and cost drivers in acquiring and maintaining licensure of childhood vaccines. In addition, when export is the goal, we describe the requirements to supply those vaccines at affordable prices to low-resource markets, including the process of World Health Organization (WHO) prequalification and supporting policy recommendation. By providing a generalized and consolidated view of these requirements we seek to build awareness in the global community of the benefits and costs associated with vaccine manufacturing and the challenges associated with maintaining consistent supply. We show that while vaccine manufacture may prima facie seem an economic growth opportunity, the complexity and high fixed costs of vaccine manufacturing limit potential profit. Further, for most lower and middle income countries a large majority of the equipment, personnel and consumables will need to be imported for years, further limiting benefits to the local economy.     

Safety of diphtheria,tetanus, acellular pertussis and inactivated poliovirus (DTaP–IPV) vaccine

Background

In 2008, a diphtheria, tetanus, acellular pertussis, and inactivated poliovirus combined vaccine (DTaP–IPV) was licensed for use in children 4 through 6 years of age. While pre-licensure studies did not demonstrate significant safety concerns, the number vaccinated in these studies was not sufficient to examine the risk of uncommon but serious adverse events.

Objective

To assess the risk of serious adverse events following DTaP–IPV vaccination.

Methods

The study was conducted from January 2009 through September 2012 in the Vaccine Safety Datalink (VSD) project. In the VSD, electronic vaccination and encounter data are updated and aggregated weekly as part of ongoing surveillance activities. Based on previous reports and biologic plausibility, eight potential adverse events were monitored: meningitis/encephalitis; seizures; stroke; Guillain–Barré syndrome; Stevens–Johnson syndrome; anaphylaxis; serious allergic reactions other than anaphylaxis; and serious local reactions. Adverse event rates in DTaP–IPV recipients were compared to historical incidence rates in the VSD population prior to 2009. Sequential probability ratio testing was used to analyze the data on a weekly basis.

Results

During the study period, 201,116 children received DTaP–IPV vaccine. Ninety-seven percent of DTaP–IPV recipients also received other vaccines on the same day, typically measles–mumps–rubella and varicella vaccines. There was no statistically significant increased risk of any of the eight pre-specified adverse events among DTaP–IPV recipients when compared to historical incidence rates.

Conclusions

In this safety surveillance study of more than 200,000 DTaP–IPV vaccine recipients, there was no evidence of increased risk for any of the pre-specified adverse events monitored. Continued surveillance of DTaP–IPV vaccine safety may be warranted to monitor for rare adverse events, such as Guillain–Barré syndrome.     

Human papillomavirus vaccine communication: Perspectives of 11–12 year-old girls,mothers, and clinicians

Objectives

Because little is known about the content of human papillomavirus (HPV) vaccine-related discussions with young adolescent girls in clinical settings, we explored communication between 11- and 12 year-old girls, mothers, and clinicians regarding HPV vaccines and concordance in reports of maternal and clinician communication.

Methods

We conducted individual interviews with 33 girls who had received the quadrivalent HPV vaccine in urban and suburban clinical settings, their mothers, and their clinicians. Data were analyzed using qualitative methods.

Results

From the perspectives of both girls and mothers, clinicians and parents were the preferred sources of HPV vaccine information for girls. Vaccine efficacy and risks/benefits of vaccination were the most commonly reported desired and actual topics of discussion by mothers, girls, and clinicians. Clinician recommendation of vaccination was reported by nearly one-fifth of girls and nearly half of mothers. The most common concordant messages were related to efficacy of the vaccine, with concordance in 70% of triads. The most common discordant messages were related to sexual health. Approximately half of clinicians (16) reported discussing sexual health, but only 5 mothers (15%) and 4 girls (12%) reported this. Triads recruited from suburban (vs. urban) practices had higher degrees of concordance in reported vaccination communication.

Conclusions

HPV vaccine efficacy and safety are important topics for clinicians to discuss with both girls and mothers; educating mothers is important because parents are a preferred source of vaccine-related information for girls. Because girls may be missing important vaccine-related messages, they should be encouraged to actively engage in vaccine discussions.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 18–49 years of age,naive to 23-valent pneumococcal polysaccharide vaccine

BackgroundBased on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60–64 years of age have been published. The same study also included a cohort of adults aged 18–49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18–49 years of age compared with adults 60–64 years of age for whom PCV13 is approved.MethodsAdults naive to PPSV23 were grouped by age into 2 cohorts: 18–49 years (n = 899; further stratified by age into 3 subgroups 18–29, 30–39, and 40–49 years) and 60–64 years (n = 417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated.ResultsIn adults aged 18–49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60–64 years. Immune responses were highest in the youngest age subgroup (18–29 years). Local reactions and systemic events were more common in adults 18–49 years compared with 60–64 years and were self-limited.ConclusionImmune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections.     

Safety and immunogenicity of pneumococcal protein vaccine candidates: Monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA–pneumococcal histidine triad protein D vaccine

Background

Pneumococcal vaccines based on protein antigens may provide expanded protection against Streptococcus pneumoniae.

Objective

To evaluate safety and immunogenicity in adults of pneumococcal vaccine candidates comprising S. pneumoniae pneumococcal histidine triad protein D (PhtD) and pneumococcal choline-binding protein A (PcpA) in monovalent and bivalent formulations.

Methods

This was a phase I, randomized, observer-blinded, placebo-controlled, step-wise dose-escalation study. Following a pilot safety study in which participants received one intramuscular injection of either aluminum hydroxide (AH)–adjuvanted PcpA (25 μg) or PhtD–PcpA (10 μg each), participants in the main study received AH–adjuvanted PcpA (25 μg), AH–adjuvanted PhtD–PcpA (10, 25, or 50 μg each), unadjuvanted PhtD–PcpA (25 μg each), or placebo as 2 injections 30 days apart. Assignment of successive dose cohorts was made after blinded safety reviews after each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD and anti-PcpA antibodies (ELISA).

Results

Six adults 18–50 years of age were included in the pilot study and 125 in the main study. No obvious increases in solicited reactions or unsolicited AEs were reported with escalating doses (adjuvanted vaccine) after either injection, or with repeated administration. Adjuvanted vaccine candidates were associated with a higher incidence of solicited reactions (particularly injection site reactions) than unadjuvanted vaccine candidates. However, no SAE or discontinuation due to an AE occurred. Geometric mean concentrations of anti-PhtD IgG and anti-PcpA IgG increased significantly after injection 2 compared with injection 1 at each dose level. No enhancement of immune responses was shown with adjuvanted vaccine candidates compared with the unadjuvanted vaccine candidate. In the dose-escalating comparison, a plateau effect at the 25 μg dose was observed as measured by geometric mean concentrations and by fold increases.

Conclusions

Promising safety profiles and immunogenicity of these monovalent and bivalent protein vaccine candidates were demonstrated in an adult population (ClinicalTrials.gov registry no. NCT01444339).     

Management and outcome of Bacille Calmette-Guérin vaccine adverse reactions

BackgroundBacille Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines globally. Management of local BCG complications (injection site reactions and suppurative or non-suppurative lymphadenitis) varies between clinicians, and the optimal approach remains uncertain.AimTo determine the clinical features, management and outcome of BCG complications at two large acute hospitals in London, United Kingdom.MethodsAll children presenting with complications of BCG vaccination between January 2008 and December 2013 were included in this observational study. Medical and electronic laboratory records were reviewed to determine clinical features, treatment and outcome.ResultsSixty children presented with adverse reactions. Two-thirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications and two children (3%) presented with both injection site reaction and lymphadenitis; only one child (2%) had disseminated BCG disease. The majority (88%) of children with injection site reactions were managed conservatively; overall, 95% showed complete resolution within 6 months. Among children with lymphadenitis, 46% were managed conservatively, whilst 54% had anti-tuberculous therapy and/or a procedure (aspiration mostly, or surgery); complete resolution was seen in 59% of cases.ConclusionsInjection site reactions and non-suppurative lymphadenitis were generally managed conservatively, with good outcomes. There was more variation in management and outcome of suppurative lymphadenitis and the optimal approach remains uncertain.     

A social vaccine? Social and structural contexts of HIV vaccine acceptability among most-at-risk populations in Thailand

Abstract

A safe and efficacious preventive HIV vaccine would be a tremendous asset for low- and middle-income country (LMIC) settings, which bear the greatest global impact of AIDS. Nevertheless, substantial gaps between clinical trial efficacy and real-world effectiveness of already licensed vaccines demonstrate that availability does not guarantee uptake. In order to advance an implementation science of HIV vaccines centred on LMIC settings, we explored sociocultural and structural contexts of HIV vaccine acceptability among most-at-risk populations in Thailand, the site of the largest HIV vaccine trial ever conducted. Cross-cutting challenges for HIV vaccine uptake – social stigma, discrimination in healthcare settings and out-of-pocket vaccine cost – emerged in addition to population-specific barriers and opportunities. A ‘social vaccine’ describes broad sociocultural and structural interventions – culturally relevant vaccine promotion galvanised by communitarian norms, mitigating anti-gay, anti-injecting drug user and HIV-related stigma, combating discrimination in healthcare, decriminalising adult sex work and injecting drug use and providing vaccine cost subsidies – that create an enabling environment for HIV vaccine uptake among most-at-risk populations. By approaching culturally relevant social and structural interventions as integral mechanisms to the success of new HIV prevention technologies, biomedical advances may be leveraged in renewed opportunities to promote and optimise combination prevention.     

Immunogenicity and safety of diphtheria–tetanus vaccine in pre-adolescent and adolescent South Koreans

This study was conducted to compare the immunogenicity and safety of diphtheria–tetanus (Td) vaccine between pre-adolescents aged 11–12 years and adolescents aged 13–18 years. A total of 277 subjects (132 pre-adolescents and 145 adolescents) participated. After vaccination, all subjects (100%) in both groups exhibited seroprotective antibody levels (≥0.1 IU/mL) against diphtheria or tetanus toxoids. Although local adverse events following vaccination were more frequently observed in the pre-adolescent group than in the adolescent group (p = 0.006), these events resolved within 7 days. Our study shows Td vaccination at age 11–12 years to be immunogenic and tolerable.     

Evaluation of effectiveness,safety and cost-benefit of the 23– valent pneumococcal capsular polysaccharide vaccine for HIV-Infected patients

IntroductionDue to the lack of understanding of the protective effects and safety of 23-valent pneumococcal polysaccharide vaccine (PPV23) in immune-deficient populations, the vaccination rate of PPV23 among HIV-infected patients is still very low in China. The main objectives of this study were to determine whether the efforts to assess measures for the prevention of pneumococcal pneumonia are still worthwhile, and provide designated vaccination program of HIV-infected persons for government policy based on.Methods60 HIV-infected adults in Lanshan county who had never been vaccinated with any pneumococcal vaccine were enrolled in this study, voluntary vaccination of PPV23 and One-year follow-up after vaccination can be completed.Result76.67% patients (46/60) had serologic response at 12 months after vaccine, CD4 count(≤500 cells/ul or > 500 cells/ul) and Month from diagnosis to first antiviral therapy (≤1 month or > 1 month) were related to antibody responses (p < 0.05).In this study, PPV23 was well tolerated, no adverse reaction was reported.11 Streptococcus pneumoniae pneumonia (9.17%,11/120) occurred in the Unvaccinated group and 1 case(1.67%,1/60)in the vaccination group within one year after vaccination(Fisher's exact probability, P = 0.225). The VE was 81.79%. The per capita benefit was 39.32 dollars, the benefit-cost ratio = 1.19. There are significant statistical differences between the vaccinated group and the non-vaccinated group in outpatient costs (p < 0.05, 95 %CI: 9.29–32.11), Medicine costs (p = 0.017, 95 %CI: 2.47–24.44), and disease related indirect costs (p = 0.038, 95 %CI: 0.93–33.63) within one year of vaccination.ConclusionOur study results showed that PPV23 can be safely and effectively administered to HIV-1 infected individuals and effectively preventing Streptococcal pneumonia. Considering the cost-benefit of vaccination among HIV-infected persons, as it has been reported in our study, it is necessary to promote the widespread use of the vaccine among HIV-infected persons in the future.     

Immunogenicity and safety of a two-dose regimen of a combined measles, mumps, rubella and varicella live vaccine (ProQuad(®)) in infants from 9 months of age

Vaccination against measles, mumps, rubella and varicella (MMRV) is currently recommended in developed countries for infants from 12 months of age. However, measles vaccination at 9 months of age is recommended by the WHO in the Expanded Program on Immunization (EPI) schedule and it is therefore possible that MMR or MMRV vaccines might also be given at this age.     

An open-label, randomized, multi-center study of the immunogenicity and safety of DTaP-IPV (Kinrix™) co-administered with MMR vaccine with or without varicella vaccine in healthy pre-school age children

Background

In the US, it is recommended that 4-6 year old children receive diphtheria-tetanus-acellular pertussis (DTaP), inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella (V), and influenza vaccines. Data relating to the concomitant administration of combination DTaP-IPV vaccine (Kinrix™; GlaxoSmithKline Biologicals) and influenza or V vaccines are currently limited. This study was undertaken to evaluate the immunogenicity and reactogenicity of Kinrix™ when co-administered with MMR (M-M-RII^®, Merck & Co.) and Varivax™ (Merck & Co.) in 4-6 year old children.

Methods

Phase IIIb, open-label, non-inferiority study (NCT00871117). We randomized (1:1) healthy 4-6 year olds to receive Kinrix™ + MMR + V on day 0 (Group 1), or Kinrix™ + MMR on day 0, followed by V at month 1 (Group 2). We measured DTaP-IPV immunogenicity before and 1 month post-vaccination (prior to V vaccination in Group 2). We collected local and general solicited symptoms within 4 days after vaccination and serious adverse events (SAEs) through 6 months post-vaccination.

Results

We enrolled 478 subjects. One month post-vaccination, >95% of subjects in both groups had booster responses to diphtheria, tetanus and pertussis antigens and all subjects had seroprotective anti-poliovirus antibody titers. Immune responses in Group 1 were non-inferior to Group 2 for responses to DTaP-IPV antigens according to pre-specified criteria. Reporting of solicited local events at the DTaP-IPV site appeared to be similar between the two vaccine groups, as was reporting of solicited general adverse events within 4 days of vaccination; no vaccine related SAEs were reported.

Conclusion

Concomitant administration of varicella vaccine with Kinrix™ and MMR did not impact the immunogenicity of diphtheria, tetanus, pertussis or poliovirus antigens. Both vaccine regimens were well tolerated. These results support the co-administration of DTaP-IPV, MMR, and V vaccines in 4-6-year-old children, providing protection against multiple diseases in a timely and efficient manner.     

Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine–naïve adults 60–64 years of age

Background

Unlike free pneumococcal polysaccharide vaccines (PPSVs), pneumococcal conjugate vaccines (PCVs) induce a T–cell–dependent immune response. The study assessed potential influence of initial 13-valent PCV (PCV13) or 23-valent PPSV (PPSV23) on subsequent vaccine administrations.

Methods

We conducted a randomized, modified double-blind study in 720 pneumococcal vaccine–naïve adults 60–64 years of age. Subjects received either PCV13 at year 0 and PCV13 at year 1; PCV13 at year 0 and PPSV23 at year 1; or PPSV23 at year 0 and PCV13 at year 1. Antipneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after each vaccination.

Results

OPA titers following PPSV23 given 1 year after PCV13 (PCV13/PPSV23) (a) were noninferior for the 12 common serotypes and significantly higher for 6 of 12 common serotypes than those following only an initial PPSV23; and (b) were significantly higher for 11 of 12 common serotypes compared with PPSV23 followed by PCV13 (PPSV23/PCV13). In addition, PPSV23 followed 1 year later by PCV13 (PPSV23/PCV13) elicited significantly lower OPA titers than after only an initial dose of PCV13 for all 13 serotypes. Responses after a second vaccination with either PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for 9 of 13 and 8 of 12 common serotypes compared with the initial PCV13 dose.

Conclusion

In pneumococcal vaccine–naïve adults 60–64 years of age, an initial PCV13 augmented the antipneumococcal response to subsequent administration of PPSV23 for many of the serotypes in common to both vaccines. In contrast, an initial PPSV23 resulted in a diminished response to subsequent administration of PCV13 for all serotypes. With a relatively short 1-year interval between doses, responses after a second vaccination with PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for a majority of serotypes compared with the initial PCV13 dose, probably reflecting the need for a longer interval between vaccine administrations.ClinicalTrials.gov Identifier: NCT00574548.