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1.
Vaccine ; 40(4): 640-649, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34969541

RESUMO

Bangladesh remains cholera endemic with biannual seasonal peaks causing epidemics. At least 300,000 severe cases and over 4,500 deaths occur each year. The available oral cholera vaccineshave not yet been adopted for cholera control in Bangladesh due to insufficient number of doses available for endemic control. With a public private partnership, icddr,b initiated a collaboration between vaccine manufacturers in Bangladesh and abroad. A locally manufactured Oral Cholera Vaccine (OCV) named Cholvax became available for testing in Bangladesh. We evaluated the safety and immunogenicity of this locally produced Cholvax (Incepta Vaccine Ltd) inexpensive OCV comparatively to Shanchol (Shantha Biotechnics-Sanofi Pasteur) which is licensed in several countries. We conducted a randomized non-inferiority clinical trial of bivalent, killed oral whole-cell cholera vaccine Cholvax vs. Shanchol in the cholera-endemic area of Mirpur, Dhaka, among three different age cohorts (1-5, 6-17 and 18-45 years) between April 2016 and April 2017. Two vaccine doses were given at 14 days apart to 2,052 healthy participants. No vaccine-related serious adverse events were reported. There were no significant differences in the frequency of solicited (7.31% vs. 6.73%) and unsolicited (1.46% vs. 1.07%) adverse events reported between the Cholvax and Shanchol groups. Vibriocidal antibody responses among the overall population for O1 Ogawa (81% vs. 77%) and O1 Inaba (83% vs. 84%) serotypes showed that Cholvax was non-inferior to Shanchol, with the non-inferiority margin of -10%. For O1 Inaba, GMT was 462.60 (Test group), 450.84 (Comparator group) with GMR 1.02(95% CI: 0.92, 1.13). For O1 Ogawa, GMT was 419.64 (Test group), 387.22 (Comparator group) with GMR 1.12 (95% CI: 1.02, 1.23). Cholvax was safe and non-inferior to Shanchol in terms of immunogenicity in the different age groups. These results support public use of Cholvax to contribute for reduction of the cholera burden in Bangladesh. ClinicalTrials.gov number: NCT027425581.

2.
J Med Virol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709664

RESUMO

Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

3.
Curr Opin Immunol ; 71: 13-20, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33845349

RESUMO

Vaccines developed in high-income countries have been enormously successful in reducing the global burden of infectious diseases, saving perhaps 2.5 million lives per year, but even for successful cases, like the rotavirus vaccine, global implementation may take a decade or more. For unincentivized vaccines, the delays are even more profound, as both the supply of a vaccine from developing country manufacturers and vaccine demand from countries with the high disease burdens have to be generated in order for impact to be manifest. A number of poverty-associated infectious diseases, whose burden is greatest in low-income and middle-income countries, would benefit from appropriate levels of support for vaccine development such as Group A Streptococcus, invasive non-typhoid salmonella, schistosomiasis, shigella, to name a few. With COVID-19 vaccines we will hopefully be able to provide novel vaccine technology to all countries through a unique collaborative effort, the COVAX facility, led by the World Health Organization (WHO), Gavi, and the Coalition for Epidemic Preparedness Innovations (CEPI). Whether this effort can deliver vaccine to all its participating countries remains to be seen, but this ambitious effort to develop, manufacture, distribute, and vaccinate 60-80% of the world's population will hopefully be a lasting legacy of COVID-19.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Saúde Global , Humanos , SARS-CoV-2/imunologia
4.
Nat Med ; 27(4): 591-600, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33846611

RESUMO

Examination of the vaccine strategies and technical platforms used for the COVID-19 pandemic in the context of those used for previous emerging and reemerging infectious diseases and pandemics may offer some mutually beneficial lessons. The unprecedented scale and rapidity of dissemination of recent emerging infectious diseases pose new challenges for vaccine developers, regulators, health authorities and political constituencies. Vaccine manufacturing and distribution are complex and challenging. While speed is essential, clinical development to emergency use authorization and licensure, pharmacovigilance of vaccine safety and surveillance of virus variants are also critical. Access to vaccines and vaccination needs to be prioritized in low- and middle-income countries. The combination of these factors will weigh heavily on the ultimate success of efforts to bring the current and any future emerging infectious disease pandemics to a close.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Doenças Transmissíveis Emergentes/prevenção & controle , SARS-CoV-2/imunologia , Vacinas/imunologia , Vacinas contra Cólera/imunologia , Doenças Transmissíveis Emergentes/epidemiologia , Vacinas contra Dengue/imunologia , Acesso aos Serviços de Saúde , Humanos , Farmacovigilância , Vacinas Tíficas-Paratíficas/imunologia , Vacina contra Febre Amarela/imunologia
5.
Vaccine ; 39(22): 3067-3080, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33077299

RESUMO

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. The Modified Vaccinia Ankara (MVA) vector system is being explored as a platform for development of multiple vaccines. This paper reviews the molecular and biological features specifically of the MVA-BN vector system, followed by a template with details on the safety and characteristics of an MVA-BN based vaccine against Zaire ebolavirus and other filovirus strains. The MVA-BN-Filo vaccine is based on a live, highly attenuated poxviral vector incapable of replicating in human cells and encodes glycoproteins of Ebola virus Zaire, Sudan virus and Marburg virus and the nucleoprotein of the Thai Forest virus. This vaccine has been approved in the European Union in July 2020 as part of a heterologous Ebola vaccination regimen. The MVA-BN vector is attenuated following over 500 serial passages in eggs, showing restricted host tropism and incompetence to replicate in human cells. MVA has six major deletions and other mutations of genes outside these deletions, which all contribute to the replication deficiency in human and other mammalian cells. Attenuation of MVA-BN was demonstrated by safe administration in immunocompromised mice and non-human primates. In multiple clinical trials with the MVA-BN backbone, more than 7800 participants have been vaccinated, demonstrating a safety profile consistent with other licensed, modern vaccines. MVA-BN has been approved as smallpox vaccine in Europe and Canada in 2013, and as smallpox and monkeypox vaccine in the US in 2019. No signal for inflammatory cardiac disorders was identified throughout the MVA-BN development program. This is in sharp contrast to the older, replicating vaccinia smallpox vaccines, which have a known risk for myocarditis and/or pericarditis in up to 1 in 200 vaccinees. MVA-BN-Filo as part of a heterologous Ebola vaccination regimen (Ad26.ZEBOV/MVA-BN-Filo) has undergone clinical testing including Phase III in West Africa and is currently in use in large scale vaccination studies in Central African countries. This paper provides a comprehensive picture of the MVA-BN vector, which has reached regulatory approvals, both as MVA-BN backbone for smallpox/monkeypox, as well as for the MVA-BN-Filo construct as part of an Ebola vaccination regimen, and therefore aims to provide solutions to prevent disease from high-consequence human pathogens.


Assuntos
Vacinas contra Ebola , Vaccinia , África Ocidental , Animais , Canadá , Europa (Continente) , Camundongos , Vírus Vaccinia/genética
6.
EClinicalMedicine ; 27: 100540, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33150320

RESUMO

Background: Typhoid causes significant mortality among young children in resource-limited settings. Conjugate typhoid vaccines could significantly reduce typhoid-related child deaths, but only one WHO-prequalified typhoid conjugate vaccine exists for young children. To address this gap, we investigated the safety, immunogenicity and dose-scheduling of Vi-DT typhoid conjugate vaccine among children aged 6-23 months. Methods: In this single center, observer blind, phase II trial, participants were randomly assigned (2:2:1) to receive one or two doses of Vi-DT or comparator vaccine. Anti-Vi IgG titer and geometric mean titers (GMT) were determined at 0, 4, 24 and 28 weeks. Data were analyzed using per-protocol and immunogenicity (a subset of intention-to-treat analysis) sets. The trial is registered with ClinicalTrials.gov (NCT03527355). Findings: Between April and July 2018, 285 children were randomized; 114 received one or two doses of Vi-DT while 57 received comparator. 277 completed the study follow-up per protocol; 112 and 110 from single- and two-dose Vi-DT schedules, respectively and 55 from the placebo group were included in the per protocol analysis. Safety profile is satisfactory. Thirteen serious adverse events were reported during the 28-week follow-up, none of which were related to Vi-DT. The seroconversion rate four weeks after the first dose was 100% (95% CI 98·3-100) in Vi-DT recipients and 7·0% (95% CI 2·8-16·7) in comparator recipients (p<0·0001). Similarly, the seroconversion rate 4 weeks after the second dose was 98·2% (95% CI 93· 6-99·5) and 21·8% (95% CI 13·0-34·4) among Vi-DT and comparator groups, respectively (p<0·0001). Anti-Vi IgG GMT was significantly higher in Vi-DT than in control group at all post-vaccination visits (p<0·0001). Interpretation: Both single and two doses of Vi-DT vaccine are safe, well tolerated, and immunogenic for infants and toddlers in a moderately endemic setting.

7.
Vaccine ; 38(49): 7702-7707, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33070999

RESUMO

Several live-attenuated viral vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of live-attenuated viral vaccines. This will help key stakeholders assess potential safety issues and understand the benefit-risk of such vaccines. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed live-attenuated viral vaccines.


Assuntos
Avaliação Pré-Clínica de Medicamentos/normas , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Medição de Risco , Sociedades Científicas , Vacinas Atenuadas/farmacologia , Vacinas Virais/farmacologia
8.
Vaccine ; 38(49): 7708-7715, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-32907759

RESUMO

Many of the vaccines under development for COVID-19 involve the use of viral vectors. The Brighton Collaboration Benefit-Risk Assessment of Vaccines by Technology (BRAVATO, formerly the Viral Vector Vaccine Safety Working Group, V3SWG) working group has prepared a standardized template to describe the key considerations for the benefit-risk assessment of viral vector vaccines. This will facilitate key stakeholders to anticipate potential safety issues and interpret or assess safety data. This would also help improve communication and public acceptance of licensed viral vector vaccines.


Assuntos
Avaliação Pré-Clínica de Medicamentos/normas , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos , Animais , Vetores Genéticos , Humanos , Internet , Medição de Risco
9.
Vaccine ; 38(39): 6184-6189, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747214

RESUMO

Inactivated viral vaccines have long been used in humans for diseases of global health threat and are now among the vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of inactivated viral vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of the vaccine platform. The standardized and structured assessment provided by the template would also help to contribute to improved communication and support public acceptance of licensed inactivated viral vaccines.


Assuntos
Infecções por Coronavirus/prevenção & controle , Aprovação de Drogas/legislação & jurisprudência , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Medição de Risco , Vacinas Virais/normas , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , COVID-19 , Vacinas contra COVID-19 , Defesa Civil , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Regulamentação Governamental , Humanos , Imunogenicidade da Vacina , Cooperação Internacional , Segurança do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2 , Vacinas de Produtos Inativados , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
10.
Vaccine ; 38(35): 5734-5739, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32653276

RESUMO

Several protein vaccine candidates are among the COVID-19 vaccines in development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of such a vaccine platform. The structured and standardized assessment provided by the template would also help contribute to improved public acceptance and communication of licensed protein vaccines.


Assuntos
Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Antígenos Virais/administração & dosagem , Antígenos Virais/efeitos adversos , Antígenos Virais/imunologia , Vacinas contra COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Segurança do Paciente , Medição de Risco , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Proteínas Virais/administração & dosagem , Proteínas Virais/efeitos adversos , Proteínas Virais/imunologia , Vacinas Virais/administração & dosagem
11.
Clin Infect Dis ; 71(Suppl 2): S141-S150, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32725225

RESUMO

Control of Salmonella enterica serovar typhi (S. typhi), the agent of typhoid fever, continues to be a challenge in many low- and middle-income countries. The major transmission route of S. typhi is fecal-oral, through contaminated food and water; thus, the ultimate measures for typhoid fever prevention and control include the provision of safe water, improved sanitation, and hygiene. Considering the increasing evidence of the global burden of typhoid, particularly among young children, and the long-term horizon for sustained, effective water and sanitation improvements in low-income settings, a growing consensus is to emphasize preventive vaccination. This review provides an overview of the licensed typhoid vaccines and vaccine candidates under development, and the challenges ahead for introduction.


Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , Criança , Pré-Escolar , Humanos , Salmonella typhi , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controle , Vacinação
12.
Vaccine ; 38(34): 5556-5561, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32571717

RESUMO

Nucleic acid (DNA and RNA) vaccines are among the most advanced vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. This will facilitate the assessment by key stakeholders of potential safety issues and understanding of overall benefit-risk. The structured assessment provided by the template can also help improve communication and public acceptance of licensed nucleic acid vaccines.


Assuntos
Medição de Risco/métodos , Vacinas de DNA/efeitos adversos , Vacinas de DNA/normas , Vacinas Virais/genética , Vacinas Virais/normas , Vacinas contra COVID-19 , Infecções por Coronavirus/genética , Infecções por Coronavirus/prevenção & controle , Humanos , Opinião Pública , Medição de Risco/normas , Vacinas de DNA/genética , Vacinas Virais/efeitos adversos
13.
Lancet HIV ; 7(4): e238-e248, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32035516

RESUMO

BACKGROUND: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX B/E administration over 6 months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunological effect of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost. METHODS: RV306 is a double-blind, placebo-controlled, randomised clinical trial done at three clinical sites in Thailand. Eligible volunteers were HIV-uninfected individuals aged 20-40 years who were at low risk for HIV infection and in good health. A randomisation schedule was centrally generated with fixed sized strata for Research Institute for Health Sciences Chiang Mai and combined Bangkok clinics. Participants were randomly assigned to one of five groups and then further randomly assigned to either vaccine or placebo. All participants received the primary RV144 vaccine series at months 0, 1, 3, and 6. Group 1 received no additional boost, group 2 received additional AIDSVAX B/E and ALVAC-HIV (vCP1521) or placebo at month 12, group 3 received AIDSVAX B/E alone or placebo at month 12, group 4a received AIDSVAX B/E and ALVAC-HIV or placebo at month 15, and group 4b received AIDSVAX B/E and ALVAC-HIV or placebo at month 18. Primary outcomes were safety and tolerability of these vaccination regimens and cellular and humoral immune responses compared between the RV144 series alone and regimens with late boosts at different timepoints. Safety and tolerability outcomes were assessed by evaluating local and systemic reactogenicity and adverse events in all participants. This trial is registered at ClinicalTrials.gov (NCT01931358); clinical follow-up is now complete. FINDINGS: Between Oct 28, 2013, and April 29, 2014, 367 participants were enrolled, of whom 27 were assigned active vaccination in group 1, 102 in group 2, 101 in group 3, 52 in group 4a, 51 in group 4b, and 34 combined placebo across all the groups. No vaccine-related serious adverse events were recorded. Occurrence and severity of local and systemic reactogenicity were similar across active groups. Groups with late boosts (groups 2, 3, 4a, and 4b) had increased peak plasma IgG-binding antibody levels against gp70 V1V2 relative to group 1 vaccine recipients with no late boost (gp70 V1V2 92TH023 adjusted p<0·02 for each; gp70 V1V2 CaseA2 adjusted p<0·0001 for each). Boosting at month 12 (groups 2 and 3) did not increase gp120 responses compared with the peak responses after the RV144 priming regimen at month 6; however, boosting at month 15 (group 4a) improved responses to gp120 A244gD- D11 (p=0·0003), and boosting at month 18 (group 4b) improved responses to both gp120 A244gD- D11 (p<0·0001) and gp120 MNgD- D11 (p=0·0016). Plasma IgG responses were significantly lower among vaccine recipients boosted at month 12 (pooled groups 2 + 3) than at month 15 (group 4a; adjusted p<0·0001 for each, except for gp70 V1V2 CaseA2, p=0·0142) and at month 18 (group 4b; all adjusted p<0·001). Boosting at month 18 versus month 15 resulted in a significantly higher plasma IgG response to gp120 antigens (all adjusted p<0·01) but not gp70 V1V2 antigens. CD4 functionality and polyfunctionality scores after stimulation with HIV-1 Env peptides (92TH023) increased with delayed boosting. Groups with late boosts had increased functionality and polyfunctionality scores relative to vaccine recipients with no late boost (all adjusted p<0·05, except for the polyfunctionality score in group 1 vs group 4b, p<0·01). INTERPRETATION: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and might improve the efficacy of preventing HIV acquisition. FUNDING: US National Institute of Allergy and Infectious Diseases and US Department of the Army.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Infecções por HIV/prevenção & controle , Vacinas contra a AIDS/imunologia , Adulto , Método Duplo-Cego , Feminino , HIV/genética , HIV/imunologia , Infecções por HIV/virologia , Humanos , Imunização Secundária , Masculino , Tailândia , Adulto Jovem
14.
JCI Insight ; 5(2)2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-31996483

RESUMO

In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope-specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti-HIV-1 effector functions.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Anti-HIV/imunologia , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Vacinas contra a AIDS/química , Anticorpos Monoclonais/química , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Citotoxicidade Celular Dependente de Anticorpos , Ensaios Clínicos como Assunto , Epitopos/genética , Epitopos/imunologia , Anticorpos Anti-HIV/química , Anticorpos Anti-HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Humanos , Imunização Secundária , Modelos Moleculares , Mutação , Conformação Proteica , Vacinas Virais , Difração de Raios X , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
15.
Hum Vaccin Immunother ; 16(1): 42-50, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31339792

RESUMO

Cholera remains a public health threat among the least privileged populations and regions affected by conflicts and natural disasters. Together with Water, Sanitation and Hygiene practices, use of oral cholera vaccines (OCVs) is a key tool to prevent cholera. Bivalent whole-cell killed OCVs have been extensively used worldwide and found effective in protecting populations against cholera in endemic and outbreak settings. No cholera vaccine had been available for United States (US) travelers at risk for decades until 2016 when CVD 103-HgR (Vaxchora™), an oral live attenuated vaccine, was licensed by the US FDA. A single dose of Vaxchora™ protected US volunteers against experimental challenge 10 days and 3 months after vaccination. However, use of Vaxchora™ poses several challenges in resource poor settings as it requires reconstitution, is age-restricted to 18 to 64 years, has no data in populations endemic for cholera, and faces challenges related to cold chain and cost.


Assuntos
Vacinas contra Cólera/imunologia , Vacinas contra Cólera/normas , Cólera/prevenção & controle , Administração Oral , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Qualidade de Produtos para o Consumidor , Surtos de Doenças/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
16.
Vaccine ; 38(28): 4476-4483, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-31585725

RESUMO

BACKGROUND: Typhoid fever remains an important public health problem in developing countries and is endemic in many parts of Asia and Africa where the incidence of disease typically peaks in school-aged children. Age restrictions and other limitations of existing oral live-attenuated typhoid and parenteral Vi polysaccharide vaccines have triggered the development of Vi conjugate vaccines with improved immunological properties, use in younger age range, and longer durability of protection. We present the safety, reactogenicity, and immunogenicity data from a Phase II study after a single dose of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) conducted in 6-23-month old Filipino children. METHODS: This is a randomized, observer-blinded Phase II study to assess the immunogenicity, safety and reactogenicity of Vi-DT compared to placebo, conducted in Muntinlupa City, The Philippines. Participants aged 6-23 months were enrolled and randomized to Vi-DT (25 µg) or placebo (0.9% sodium chloride) and evaluated for immunogenicity and overall safety 28 days post vaccination. RESULTS: A total of 285 participants were enrolled and age-stratified: 6 to < 9 months, 9-12 months, and 13-23 months. Seventy-six (76) participants received Vi-DT and 19 received placebo per each strata. All participants seroconverted after a single dose of Vi-DT versus 7% of placebo recipients. Anti-Vi IgG GMT was 444.38 [95% CI (400.28; 493.34)] after a single dose of Vi-DT; there was no change in GMT after placebo administration, 0.41 [95% CI (0.33; 0.51), p < 0.0001]. A similar pattern of immunogenicity was reported across all age strata. The vaccine reported to be safe and well tolerated. CONCLUSIONS: Vi-DT vaccine was immunogenic, safe, and well tolerated in children aged 6-23 months. ClinicalTrials.gov registration number: NCT03527355.


Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas/imunologia , África , Anticorpos Antibacterianos , Ásia , Pré-Escolar , Vacina contra Difteria e Tétano , Humanos , Imunogenicidade da Vacina , Lactente , Filipinas , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/efeitos adversos , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia
17.
Vaccine ; 38(7): 1753-1761, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31879124

RESUMO

We have earlier reported that a single dose of oral cholera vaccine (OCV) is protective in adults and children ≥5 years of age and sustained for 2 years. We enrolled participants (n = 240) from this study, between March-September 2017, over 3 years after receiving a primary single dose. Immune responses were measured in placebo group (Primary Immunization group: PI) and compared with those who received a single dose (Booster Immunization group: BI). The children were 4 to <5 years, 5 to <18 years and adults >18 years. Blood was collected at day 0 (before vaccination) and after receiving 1st and 2nd doses of OCV. Overall, the BI and PI groups showed vibriocidal antibody response after 1st and 2nd dose of vaccination in all age groups to V. cholerae O1 and O139. Young children in the BI group showed significantly higher vibriocidal antibody response two weeks after receiving the first dose as compared to PI group to LPS. Elevated plasma IgA responses to LPS after the first dose were observed among the BI group compared to the PI group among the young children. Mucosal antibody responses measured in fecal extracts showed similar increases as that of vibriocidal and LPS responses in the BI group. These results suggest a single boosting dose of OCV generated immune response in primed population >5 years of age who had earlier received OCV. However, young children who had received OCV earlier, boosting after a single dose, resulted in increased immune responses compared to the PI group. Further studies are needed to assess protection obtained from different strategies, especially for young children and to determine the numbers of primary and booster doses needed. In addition, more information is needed regarding the optimum interval between primary and booster doses to plan future interventions for cholera control. ClinicalTrials.gov Identifier: NCT02027207.


Assuntos
Vacinas contra Cólera/imunologia , Cólera , Imunização Secundária , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Criança , Pré-Escolar , Cólera/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacinação , Adulto Jovem
18.
Vaccine ; 38 Suppl 1: A118-A126, 2020 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-31879125

RESUMO

Cholera remains a major global public health problem that is primarily linked to insufficient access to safe water and proper sanitation. Oral Cholera Vaccine (OCV) has been recommended as an additional public health tool along with WASH in cholera endemic countries and in areas at risk for outbreaks. The new generation OCV is safe and offers good protection in older children and adults while limited protection in younger children less than five years of age has been observed. The combination of direct vaccine protection and vaccine herd immunity effects makes OCV highly cost-effective and, therefore, attractive for use in developing countries. Additionally, in recent studies OCV was safe in pregnant women, supporting its use in pregnant women in cholera endemic countries. However, knowledge need to be developed for current vaccines for their prolonged duration of protection and vaccines need improvements for better immune response in younger children. A single dose vaccination regimen would be more cost-effective and easier to deliver. Recent approaches have focused on designing genetically attenuated cholera strains for use in single-dose cholera vaccines. The global demand for OCV has been boosted by the WHO recommendation to use OCV and is driven largely by epidemics and outbreaks and has been increasing due to the availability of cheaper easy-to-use vaccines, feasibility of mass OCV vaccination campaigns, demonstration of protection to underserved population in precarious situations, and vaccine costs being borne by Gavi (Vaccine Alliance). For rapid access in emergency and equitable distribution of OCV in cholera-endemic low-income countries, a global OCV stockpile was established in 2013 with support from the Global Alliance for Vaccines and Immunization. The three WHO-prequalified vaccines are Dukoral®, Shanchol™, Euvichol® (and Euvichol® Plus presentation), the latter two being included in the stockpile.


Assuntos
Vacinas contra Cólera/administração & dosagem , Cólera , Administração Oral , Adulto , Criança , Cólera/epidemiologia , Cólera/prevenção & controle , Surtos de Doenças , Feminino , Humanos , Gravidez , Vacinação , Vacinas Atenuadas/administração & dosagem
19.
J Virol ; 94(4)2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31776278

RESUMO

Induction of protective antibodies is a critical goal of HIV-1 vaccine development. One strategy is to induce nonneutralizing antibodies (NNAbs) that kill virus-infected cells, as these antibody specificities have been implicated in slowing HIV-1 disease progression and in protection. HIV-1 Env constant region 1 and 2 (C1C2) monoclonal antibodies (MAbs) frequently mediate potent antibody-dependent cellular cytotoxicity (ADCC), making them an important vaccine target. Here, we explore the effect of delayed and repetitive boosting of RV144 vaccine recipients with AIDSVAX B/E on the C1C2-specific MAb repertoire. It was found that boosting increased clonal lineage-specific ADCC breadth and potency. A ligand crystal structure of a vaccine-induced broad and potent ADCC-mediating C1C2-specific MAb showed that it bound a highly conserved Env gp120 epitope. Thus, boosting to affinity mature these types of IgG C1C2-specific antibody responses may be one method by which to make an improved HIV vaccine with higher efficacy than that seen in the RV144 trial.IMPORTANCE Over one million people become infected with HIV-1 each year, making the development of an efficacious HIV-1 vaccine an important unmet medical need. The RV144 human HIV-1 vaccine regimen is the only HIV-1 clinical trial to date to demonstrate vaccine efficacy. An area of focus has been on identifying ways by which to improve upon RV144 vaccine efficacy. The RV305 HIV-1 vaccine regimen was a follow-up boost of RV144 vaccine recipients that occurred 6 to 8 years after the conclusion of RV144. Our study focused on the effect of delayed boosting in humans on the vaccine-induced Env constant region 1 and 2 (C1C2)-specific antibody repertoire. It was found that boosting with an HIV-1 Env vaccine increased C1C2-specific antibody-dependent cellular cytotoxicity potency and breadth.


Assuntos
Vacinas contra a AIDS/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Anticorpos Monoclonais/imunologia , Formação de Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Epitopos/imunologia , Anticorpos Anti-HIV/imunologia , Anticorpos Anti-HIV/ultraestrutura , Proteína gp120 do Envelope de HIV/ultraestrutura , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Imunização Secundária/métodos , Imunoglobulina G/imunologia
20.
Clin Infect Dis ; 69(Suppl 6): S499-S509, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665782

RESUMO

BACKGROUND: Analyses of the global spatial and temporal distribution of enteric fever outbreaks worldwide are important factors to consider in estimating the disease burden of enteric fever disease burden. METHODS: We conducted a global literature review of enteric fever outbreak data by systematically using multiple databases from 1 January 1990 to 31 December 2018 and classified them by time, place, diagnostic methods, and drug susceptibility, to illustrate outbreak characteristics including spatial and temporal patterns. RESULTS: There were 180 940 cases in 303 identified outbreaks caused by infection with Salmonella enterica serovar Typhi (S. Typhi) and Salmonella enterica serovar Paratyphi A or B (S. Paratyphi). The size of outbreak ranged from 1 to 42 564. Fifty-one percent of outbreaks occurred in Asia, 15% in Africa, 14% in Oceania, and the rest in other regions. Forty-six percent of outbreaks specified confirmation by blood culture, and 82 outbreaks reported drug susceptibility, of which 54% had multidrug-resistant pathogens. Paratyphoid outbreaks were less common compared to typhoid (22 vs 281) and more prevalent in Asia than Africa. Risk factors were multifactorial, with contaminated water being the main factor. CONCLUSIONS: Enteric fever outbreak burden remains high in endemic low- and middle-income countries and, despite its limitations, outbreak data provide valuable contemporary evidence in prioritizing resources, public health policies, and actions. This review highlights geographical locations where urgent attention is needed for enteric fever control and calls for global action to prevent and contain outbreaks.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Saúde Global , Febre Paratifoide/epidemiologia , Análise Espaço-Temporal , Febre Tifoide/epidemiologia , África/epidemiologia , Antibacterianos/farmacologia , Ásia/epidemiologia , Efeitos Psicossociais da Doença , Humanos , Febre Paratifoide/diagnóstico , Prevalência , Salmonella paratyphi A/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/diagnóstico
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