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Clinical Microbiology and Infection :... Dec 2019Epidemiological and immunological studies are increasingly reporting non-specific effects (NSEs) of vaccines; i.e. vaccines may affect the risk and severity of... (Review)
Review
BACKGROUND
Epidemiological and immunological studies are increasingly reporting non-specific effects (NSEs) of vaccines; i.e. vaccines may affect the risk and severity of non-targeted infections. We reviewed how epidemiological studies developed the concept of beneficial NSEs of live vaccines.
SOURCES
This is a personal narrative of how we came to pursue the concept of NSEs in studies of measles vaccine (MV) from the late 1970s. We also searched Pubmed for epidemiological studies of nonspecific/non-specific effects (NSEs) of the most common human vaccines.
CONTENT
When smallpox vaccine was introduced around 1800, bacillus Calmette-Guérin (BCG) against tuberculosis in the 1920s and oral polio vaccine (OPV) in the 1960s, there were suggestions that these live attenuated vaccines reduced mortality more than expected. However, scientific follow-up was limited and the concept of beneficial NSEs did not become mainstream. We observed beneficial NSEs after MV was introduced in low-income countries in the 1970s. Subsequent observational studies and randomized trials confirmed beneficial NSEs of smallpox vaccine, BCG and OPV. Recently, beneficial NSEs have been claimed for the non-live diphtheria-tetanus-pertussis and rabies vaccines. However, no non-live vaccine has yet been documented to produce beneficial NSEs.
IMPLICATIONS
Observational and experimental research has shown beneficial NSEs of four live attenuated vaccines: smallpox vaccine, BCG, OPV and MV. With immunological evidence now supporting the epidemiological observations, it is urgent to take both the specific and NSEs into account in the planning of vaccination programmes.
Topics: Clinical Studies as Topic; Cross Protection; Female; Humans; Male; Mortality; Sex Factors; Vaccination; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 31449870
DOI: 10.1016/j.cmi.2019.08.011 -
Frontiers in Cellular and Infection... 2020Plague, which is caused by , is one of the most dangerous infectious diseases. No FDA-approved vaccine against plague is available for human use at present. To improve...
Plague, which is caused by , is one of the most dangerous infectious diseases. No FDA-approved vaccine against plague is available for human use at present. To improve the immune safety of EV76 based live attenuated vaccine and to explore the feasibility of aerosolized intratracheal inoculation (i.t.) route for vaccine delivery, a plasminogen activator protease () gene deletion mutant of the attenuated strain EV76-B-SHU was constructed, and its residual virulence and protective efficacy were evaluated in a mouse model via aerosolized intratracheal inoculation (i.t.) or via subcutaneous injection (s.c.). The residual virulence of EV76-B-SHUΔ was significantly reduced compared to that of the parental strain EV76-B-SHU following i.t. and s.c. infection. The EV76-B-SHUΔ induced higher levels of mucosal antibody sIgA in the bronchoalveolar lavage fluid of mice immunized by i.t. but not by s.c.. Moreover, after lethal challenge with biovar Microtus strain 201 (avirulent in humans), the protective efficacy and bacterial clearance ability of the EV76-B-SHUΔ-i.t. group were comparable to those of the EV76-B-SHUΔ-s.c. and EV76-B-SHU immunized groups. Thus, the EV76-B-SHUΔ represents an excellent live-attenuated vaccine candidate against pneumonic plague and aerosolized i.t. represents a promising immunization route in mouse model.
Topics: Animals; Disease Models, Animal; Mice; Plague; Plague Vaccine; Vaccines, Attenuated; Yersinia pestis
PubMed: 33014895
DOI: 10.3389/fcimb.2020.00473 -
Vaccine Jan 2015The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry... (Review)
Review
The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle.
Topics: Animals; Cattle; Drug Carriers; Drug Discovery; Genetic Vectors; Immunity, Cellular; Immunity, Humoral; Mastadenovirus; Vaccines, Attenuated; Vaccines, Synthetic; Veterinary Medicine
PubMed: 25498212
DOI: 10.1016/j.vaccine.2014.11.055 -
Human Vaccines & Immunotherapeutics 2014Two live, attenuated hepatitis A vaccines, H 2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C... (Review)
Review
Two live, attenuated hepatitis A vaccines, H 2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H 2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of the H 2 strain or for marmoset-to-marmoset transmission of LA-1 strain, by close contact. H 2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in China for 14 years following introduction of the H 2 live vaccine into the Expanded Immunization Program (EPI) in 1992.
Topics: Administration, Oral; China; Disease Eradication; Hepatitis A; Hepatitis A Antibodies; Hepatitis A Vaccines; Hepatitis A virus; Humans; Immunization Programs; Injections, Subcutaneous; Serial Passage; Temperature; Vaccination; Vaccines, Attenuated
PubMed: 24280971
DOI: 10.4161/hv.27124 -
Infection and Immunity Aug 2016Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective...
Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain.
Topics: Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Vaccines; Burkholderia mallei; Disease Models, Animal; Female; Glanders; Immunization; Immunization, Secondary; Immunocompromised Host; Immunoglobulin G; Mice; Mutation; Vaccines, Attenuated
PubMed: 27271739
DOI: 10.1128/IAI.00328-16 -
Emerging Microbes & Infections Sep 2018H7N9 influenza viruses emerged in 2013 and have caused severe disease and deaths in humans in China. Some H7N9 viruses circulating in chickens have mutated to highly...
H7N9 influenza viruses emerged in 2013 and have caused severe disease and deaths in humans in China. Some H7N9 viruses circulating in chickens have mutated to highly pathogenic viruses that have caused several disease outbreaks in chickens. Studies have shown that when the H7N9 highly pathogenic viruses replicate in ferrets or humans, they easily acquire certain mammalian-adapting mutations and become highly lethal in mice and highly transmissible in ferrets by respiratory droplet, creating the potential for human-to-human transmission. Therefore, the development of effective control measures is a top priority for H7N9 pandemic preparedness. In this study, we evaluated the protective efficacy of a cold-adapted, live attenuated H7N9 vaccine (H7N9/AAca) against two heterologous H7N9 highly pathogenic viruses in mice and guinea pigs. Our results showed that one dose of the H7N9/AAca vaccine prevented disease and death in mice challenged with two different H7N9 highly pathogenic viruses, but did not prevent replication of the challenge viruses; after two doses of H7N9/AAca, the mice were completely protected from challenge with A/chicken/Hunan/S1220/2017(H7N9) virus, and very low viral titers were detected in mice challenged with H7N9 virus CK/SD008-PB2/627 K. More importantly, we found that one dose of H7N9/AAca could efficiently prevent transmission of CK/SD008-PB2/627 K in guinea pigs. Our study suggests that H7N9/AAca has the potential to be an effective H7N9 vaccine and should be evaluated in humans.
Topics: Animals; China; Disease Models, Animal; Female; Ferrets; Guinea Pigs; Humans; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Influenza, Human; Mice; Mice, Inbred BALB C; Vaccines, Attenuated; Virulence; Virus Replication
PubMed: 30206210
DOI: 10.1038/s41426-018-0154-6 -
The New England Journal of Medicine Feb 2007Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. To evaluate... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. To evaluate alternative vaccine approaches, we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children.
METHODS
Children 6 to 59 months of age, without a recent episode of wheezing illness or severe asthma, were randomly assigned in a 1:1 ratio to receive either cold-adapted trivalent live attenuated influenza vaccine (a refrigeration-stable formulation of live attenuated intranasally administered influenza vaccine) or trivalent inactivated vaccine in a double-blind manner. Influenza-like illness was monitored with cultures throughout the 2004-2005 influenza season.
RESULTS
Safety data were available for 8352 children, and 7852 children completed the study according to the protocol. There were 54.9% fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine (153 vs. 338 cases, P<0.001). The superior efficacy of live attenuated vaccine, as compared with inactivated vaccine, was observed for both antigenically well-matched and drifted viruses. Among previously unvaccinated children, wheezing within 42 days after the administration of dose 1 was more common with live attenuated vaccine than with inactivated vaccine, primarily among children 6 to 11 months of age; in this age group, 12 more episodes of wheezing were noted within 42 days after receipt of dose 1 among recipients of live attenuated vaccine (3.8%) than among recipients of inactivated vaccine (2.1%, P=0.076). Rates of hospitalization for any cause during the 180 days after vaccination were higher among the recipients of live attenuated vaccine who were 6 to 11 months of age (6.1%) than among the recipients of inactivated vaccine in this age group (2.6%, P=0.002).
CONCLUSIONS
Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing. (ClinicalTrials.gov number, NCT00128167 [ClinicalTrials.gov].).
Topics: Child, Preschool; Female; Follow-Up Studies; Hospitalization; Humans; Infant; Influenza Vaccines; Influenza, Human; Kaplan-Meier Estimate; Male; Respiratory Sounds; Treatment Outcome; Vaccines, Attenuated
PubMed: 17301299
DOI: 10.1056/NEJMoa065368 -
Vaccine Aug 2013In the aftermath of the 2001 anthrax attacks in the U.S., numerous efforts were made to increase the level of preparedness against a biological attack both in the US and... (Review)
Review
In the aftermath of the 2001 anthrax attacks in the U.S., numerous efforts were made to increase the level of preparedness against a biological attack both in the US and worldwide. As a result, there has been an increase in research interest in the development of vaccines and other countermeasures against a number of agents with the potential to be used as biological weapons. One such agent, Francisella tularensis, has been the subject of a surge in the level of research being performed, leading to a substantial increase in knowledge of the pathogenic mechanisms of the organism and the induced immune responses. This information has facilitated the development of multiple new Francisella vaccine candidates. Herein we review the latest live attenuated F. tularensis vaccine efforts. Historically, live attenuated vaccines have demonstrated the greatest degree of success in protection against tularemia and the greatest promise in recent efforts to develop of a fully protective vaccine. This review summarizes recent live attenuated Francisella vaccine candidates and the lessons learned from those studies, with the goal of collating known characteristics associated with successful attenuation, immunogenicity, and protection.
Topics: Bacterial Vaccines; Biological Warfare Agents; Francisella tularensis; Humans; Tularemia; Vaccines, Attenuated
PubMed: 23764535
DOI: 10.1016/j.vaccine.2013.05.096 -
The Journal of Infectious Diseases Jul 2017Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal...
Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of immunoglobulin G and immunoglobulin A to all antigens tested, while causing no adverse symptoms or leukocytosis. When BPZE1-vaccinated baboons were challenged with a high dose of a highly virulent B. pertussis isolate, they were fully protected against disease, whereas naive baboons developed illness (with 1 death) and leukocytosis. Total postchallenge nasopharyngeal virulent bacterial burden of vaccinated animals was substantially reduced (0.002%) compared to naive controls, providing promising evidence in nonhuman primates that BPZE1 protects against both pertussis disease and B. pertussis infection.
Topics: Animals; Antibodies, Bacterial; Antigens, Bacterial; Bordetella pertussis; Disease Models, Animal; Immunoglobulin A; Immunoglobulin G; Models, Molecular; Papio; Pertussis Vaccine; Vaccines, Attenuated; Whooping Cough
PubMed: 28535276
DOI: 10.1093/infdis/jix254 -
The New England Journal of Medicine Jan 2006The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.
METHODS
We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients).
RESULTS
The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78).
CONCLUSIONS
Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)
Topics: Administration, Oral; Diarrhea, Infantile; Double-Blind Method; Female; Gastroenteritis; Hospitalization; Humans; Incidence; Infant; Intussusception; Male; Risk; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Survival Analysis; Vaccines, Attenuated
PubMed: 16394298
DOI: 10.1056/NEJMoa052434