Polyvalent Vaccine Research Articles

Evaluation of specific and non-specific immune response of four vaccines for caseous lymphadenitis in sheep challenged.

Background:Caseous lymphadenitis (CLA) is a serious disease affects sheep and goat, caused by Corynebacterium pseudotuberculosis. Due to it is non-treatable disease, so the effective preventive vaccines are considered a significant way to combat the disease. All strains of C. pseudotuberculosis have several virulence factors that associated with their cell invasion, survival, and proliferation such as phospholipase D (PLD), outer lipid coat, and secreted proteases.Aim:The present study was directed to perform a comparative innate and acquired immune response assessment of different four vaccine formulas to evoke protection against induced (CLA) challenge in sheep.Materials and Methods:Negative ELISA (free of CLA) 15 local breed male (Balady) sheep were divided into five groups, each has received a different vaccine while the control has received saline buffer. The first vaccine composed of toxoid PLD alone the second composed of toxoid PLD with bacterin (formalinkilled bacteria), the third vaccine composed of toxoid PLD plus covaccine 8, while the fourth one composed of toxoid PLD plus locally produced polyvalent clostridial vaccine. The specific immune response was evaluated through lymphocyte proliferation assay using ELISA BrdU kit, while the non-specific response was estimated by superoxide anion production and lysozyme activity assays.Results:The study revealed that PLD toxoid could evoke the highest specific immune response, showing a stimulation index (9.12%). On the other hand, combined toxoid ↱PLD with bacterin followed by PLD toxoid showed a significant increase in the non-specific innate immune response.Conclusion:The present study indicated that the toxoid PLD alone vaccine was most efficient and provided innate and acquired immune response in animals against CLA.

Elimination of Epidemic Meningitis in the African Region: Progress and Challenges:2010-2016

Epidemics of meningococcal disease constitute a major public health challenge in Africa, affecting mostly the 24 countries of the meningitis belt. These epidemics led to a call for a call for a safe, effective and affordable conjugate vaccine against the major serogroup responsible for recent epidemics by leaders of the region. This paper documents experiences with efforts at eliminating epidemic meningitis in the African Region. The meningoccocal serogroup A conjugate vaccine was developed, licensed and offered to more than 235 million people through mass vaccination campaigns in 16 countries since 2010. Future plans include providing the vaccine to the remaining countries in the African Meningitis Belt and, to implement the vaccine into routine national infant immunization programme and to organise catch-up immunization campaigns every 5 years for unvaccinated <5 year-olds who had missed their routine vaccinations. The success of the project is evidenced by the large declines in cases of group A meningococcal disease since 2010, with no cases reported in vaccinated persons across the 16 countries, reflecting the highly effective nature of the vaccine. The successful control of serogroup A meningococcal disease has highlighted the need to tackle other meningococcal serogroups through development of polyvalent conjugate vaccines with the aim of eliminating epidemics of meningococcal meningitis in the African region.

Antigenic potential of a recombinant polyvalent DNA vaccine against pathogenic leptospiral infection

Leptospirosis is a serious epidemic disease caused by pathogenic Leptospira species. The disease is endemic in most tropical and sub-tropical regions of the world. Currently, there is no effective polyvalent vaccine for prevention against most of the circulating serovars. Moreover, development of an efficient leptospiral vaccine capable of stimulating cross-protective immune responses against a wide range of serovars remains a daunting challenge. This, in part, is associated with the extensive diversity and variation of leptospiral serovars from region to region. In this study, a multi-epitope DNA vaccine encoding highly immunogenic epitopes from LipL32 and LipL41 was designed using in-silico approach. The DNA encoding antigenic epitopes was constructed from conserved pathogenic Leptospira genes (LipL32 and LipL41). Immunization of golden Syrian hamsters with the multi-epitope chimeric DNA vaccine resulted in the production of both agglutinating and neutralizing antibodies as evidence by MAT and in-vitro growth inhibition tests respectively. The antibodies produced reacted against eight different serovars and significantly reduced renal colonization following in vivo challenge. The vaccine was also able to significantly reduce renal colonization which is a very important factor responsible for persistence of leptospires among susceptible and reservoir animal hosts. In conclusion, the leptospiral multi-epitope chimeric DNA vaccine can serve as a potentially effective and safe vaccine against infection with different pathogenic leptospiral serovars.

Group B Streptococcus (GBS) vaccine

Intrapartum antibiotic prophylaxis (IPA) during labor for women identified as having recto-vaginal Groups B Streptococcus (GBS) colonization, has been successful in preventing early-onset invasive (<7 days of age) disease in new-borns in high income countries where implemented. Nevertheless, GBS remains a leading cause of neonatal sepsis in high-income settings, and is now also the leading cause of bacterial meningitis in USA. Also, the incidence of invasive GBS disease remains high in sub-Saharan African countries, where IAP is not feasible, whilst its contribution to neonatal sepsis is uncertain in South Asia. Furthermore, recent data indicate that the burden of GBS associated stillbirths might be similar to that for EOD in some African countries. Recent advances in the prevention of invasive GBS disease during early infancy, including the potential to prevent late onset disease (7-89 days age) which is not preventable by IAP, is the development of polyvalent polysaccharide protein conjugate vaccines. Recent studies have reported on the safety and immunogenicity of a trivalent (serotypes Ia, Ib and III) GBS polysaccharide protein conjugate vaccine (GBS-3CV). This vaccine elicits immune responses in pregnant women vaccinated during the last trimester, albeit less so among women in whom the pre-vaccination antibody titers were less than the lower detection limit of the assay. The ratio of antibody transfer to the newborns’ of these women was approximately 0.5-0.7, indicating less efficient transplacental transfer of polysaccharide targeted IgG than is observed for IgG targeted at protein antigens. Furthermore, vaccination of HIV-infected women, elicited lower quantitative antibody responses than in HIV-uninfected women, suggesting the need for different vaccine schedules in these women. Also, the GBS conjugate vaccine appears to be more immunogenic in African than European/North American women. The licensure of a GBS vaccine for pregnant women aimed at protection against invasive GBS disease of their newborns will, however, require sample size in excess of 70,000 participants for an invasive disease endpoint. An alternate licensure pathway, as is the case for meningococcal vaccine, could be premised on establishing a sero-correlate of protection against invasive disease and using this to license the vaccine based on immunogenicity and safety.

Aetiology of neonatal sepsis in Nigeria, and relevance of Group b streptococcus: A systematic review.

BackgroundGroup B Streptococcus (GBS) causes invasive infections in neonates and has been implicated as a cause of prelabour rupture of membranes, preterm delivery and stillbirths. The success of phase II trials of polyvalent polysaccharide GBS vaccines indicates that these infections are potentially preventable. Nigeria is the most populous country in Africa with one of the highest birth rates, one of the highest neonatal sepsis incidence rates and one of the highest mortality rates in the world. Therefore, before the possible introduction of preventive strategies such as intrapartum antibiotic prophylaxis or GBS vaccine into Nigeria, it is vital that there is accurate data on the aetiology of neonatal sepsis and on the incidence of GBS neonatal sepsis in particular. The objective of this study was to determine the incidence and aetiology of neonatal sepsis in Nigeria with a focus on GBS sepsis and also to assess the potential impact of a GBS vaccine.MethodsA literature search was conducted on the databases of African journals online, PubMed and Google Scholar for works conducted between 1987 to 2017. Case reports, reviews, and studies not stating specific culture methods or specific bacteria isolated were excluded. Data extracted included; incidence of neonatal sepsis, method of blood culture, blood volume, sample size, bacterial agents isolated and history of antibiotic use. PRISMA guidelines were followed and modified Down’s and Black criteria used to evaluate the quality of studies.ResultsA total of 5,114 studies were reviewed for neonatal sepsis out of which 24 consisting of a total of 2,280 cases were selected for final review. Nine studies met criteria for assessment of hospital based incidence of neonatal sepsis representing 31,305 hospital births. The incidence of neonatal sepsis was 18.2/1000 livebirths with range from 7-55/1000 livebirths while the GBS incidence was 0.06/1000 livebirths with range from 0-2/1000 live births. We discovered various limitations such as identification techniques that could result in underestimation of the true incidence of GBS sepsis. Pathogens such as Klebsiella pneumoniae and Staphylococcus aureus were more commonly isolated than GBS.Implications of key findingsThe hospital based incidence of neonatal sepsis was high at 18.2/1000 live births while that due to GBS was 0.06/1000 live births. The burden of neonatal sepsis, including that attributable to GBS is substantial and could be reduced by preventive strategies such as intrapartum antibiotic prophylaxis or GBS vaccine. There is however very sparse meaningful data currently. Well planned prospective studies with larger sample sizes, more advanced isolation and identification techniques and those following up invasive disease cases for possible short and long term sequelae are needed—not only prior to possible introduction of the vaccine to determine the baseline epidemiology, but also thereafter to monitor its impact on the population. Strategies need to be developed to also reduce the morbidity and mortality attributable to other bacteria that have an incidence even greater than that of GBS.

Use of molecular biology tools for rapid identification and characterization of Pasteurella spp.

Aim:This study aimed to create rapid characterization and genotyping of Pasteurella multocida (PM) protocol using modern molecular biology techniques.Materials and Methods:Thirty bacterial isolates were characterized by capsular and somatic identification using conventional procedure followed by multiplex polymerase chain reaction (PCR), restriction endonucleases analysis (REA), and finally confirmed by sequence analysis. Two local vaccine strains and two field isolates were identified as PM Type A and B.Results:A total of 30 isolates were found positive for PM either morphologically and biochemically; however, multiplex PCR technique identified only 22 isolates as Pasteurella species using universal primers while 8 isolates were found negative for PM. 12 of 22 isolates (54%) were characterized at the same reaction into PM Type A, five isolates (23%) were Type B and the rest five isolates (23%) of tested isolates were negative for Types A, B, and D. Hemorrhagic septicemia Type B: 2 or B: 5 could be identified somatically within PM capsular serogroup B using PCR technique. Somatic characterization of PM was done using REA that could identify all PM Type A into A:1 and all PM Type B into B: 2. These protocols were verified for its accuracy and reliability by sequence analysis of two vaccine strains of PM Type A and B that were characterized previously by biochemical and serological methods as well as two selected isolates from the 22 positive isolates representing PM Type A and B.Conclusion:PCR and REA could confirm the identity of PM and provide a rapid and reliable characterization in comparison with biochemical analysis and conventional serotyping that may take up to 2 weeks. Hence, they can reduce the time needed for polyvalent vaccine production and when the reference antisera are unavailable. Moreover, the identity of Omp-H for vaccine and field strains may provide better data to control Pasteurellosis in Egypt.

Economic impact of an outbreak of botulism in a cattle feedlot

ABSTRACT: Botulism is a febrile disease, fatal in most cases, which affects the muscles of locomotion, chewing, and swallowing, as well as the diaphragm and intercostal muscles, causing flaccid paralysis and respiratory arrest. In bovines, the etiology is due to the ingestion of neurotoxins types C and D formed by the bacterium Clostridium botulinum in an animal or vegetal substance, during decomposition. Vaccination is one of the most effective prophylactic means to prevent this disease. In this study, an outbreak of botulism was evaluated in a feedlot with 6,300 finishing cattle, wherein 25 died as a consequence of contracting this disease. The economic losses resulting from the deaths were analyzed, and economic analysis was conducted, involving the estimated cost of vaccination for the whole herd under risk, with the objective of evaluating whether this prophylactic practice is a viable action plan. The financial loss due to the deaths resulting from botulism in the case studied was found to be R$55,560.00, equivalent to 0.39% of the total monetary value of the herd. The cost of immunizing the entire herd under risk was 14.06% (for toxins exclusive to toxins C and D) and 22.22% (for polyvalent vaccines against clostridiosis) of the financial loss incurred as a consequence of the recorded deaths. It was concluded that botulism is a disease that can cause a significant economic impact on intensive livestock production systems, and that vaccination is an economically viable prophylactic action if performed with adequate sanitary planning.

Sero-prevalence of foot and mouth disease in cattle in Borena Zone, Oromia regional state, Ethiopia

ObjectiveTo determine the sero-prevalnce of FMD and indicate patterns of animal movement in Borena zone, Ethiopia.IntroductionThe Foot and mouth disease (FMD) virus is a highly contagious and economically devastating trans boundery disease of cloven-hooved domestic and wild animals1.MethodsA cross-sectional study was carried out between April and November 2015 to investigate the sero-prevalence of foot-and-mouth disease (FMD) in cattle using serology and questionnaire servey in Borena zone.ResultsA total of 363 sera samples were collected from nine peasant associations found in three different districts. An overall seroprevalence of 42.7% (95%: CI= 37.7-47.84) was found during the study. There was statistically significant difference among the districts (χ2 = 10.43, p=0.005) and the highest prevalence was found in Dire district which accounted for 52.8% (95%: CI, 44.0-61.4). Soda peasant association of Dire district and Surupa peasant association of Yabello district accounted for highest sero-prevalence 65.5% (95%: CI, 49.4-78.5) and 65.0% (95%: CI= 40.4-78.5), respectively. Statistical significant difference in footand-mouth disease seroprevalence (χ2 =31.1, p=0.000) was found among the peasant associations. Similarly, there was significance difference (χ2 =17.4, p=0.000) in the prevalence of foot-and-mouth disease between age groups. Though the seroprevalence foot-and-mouth disease was higher in females than in males, there was no significant difference (χ2=1.63, p=0.202) between sex. The different risk factors analyzed during this study indicated that, peasant associations (PAs), district and age were seen to be significantly associated (p&lt;0.05) with the seroprevalence of foot-and-mouth disease. The questionnaire survey revealed that foot-and-mouth disease outbreak was commonly seen during June to August (Short rainy season) and December to February (Long dry season), locally called Adolessa and Bona, respectively. Younger (1-3 years) animals were most susceptible than calf and adults (&gt;3years). Moreover, an extrinsic factor like dry season enforces pastoralist to travel a longer distance to look for grazing lands and water sources that creates suitable conditions for foot-and-mouth disease transmission between infected and susceptible animals.ConclusionsFMD is an important transboundery animal disease that affects the livelihood of farmers and economy of the country. In pastoral areas like Borena where livestock movement is common during dry season, the disease is devastating and spreading from one area to the other. Therefore, an extensive regular serological survey, virus isolation, and characterizations of FMD virus need to be conducted for a possible development of poly-valent vaccines that contains commonly circulating serotypes of FMD virus in Ethiopia.

Collaboratively-developed vaccine pricing and stable profit sharing mechanisms

Within the private pediatric vaccine market, we consider the problem of pricing a polyvalent vaccine developed via collaboration between manufacturers that otherwise compete for market share. This study is motivated by the joint development by Merck and Sanofi Pasteur of a hexavalent pediatric vaccine that is undergoing clinical trials for childhood immunizations in the United States. Adopting a cooperative game theoretic framework, we formulate a mixed-integer linear program and a bilevel mixed-integer nonlinear program. When solved sequentially, these mathematical programming formulations identify whether the collaborative venture begets a stable coalition of manufacturers and, if such is the case, a price for the new vaccine that maximizes the net increase in profits among the collaborating manufacturers, subject to the actions of a rational customer seeking to minimize the cost of meeting the Recommended Childhood Immunization Schedule using pediatric vaccines available in the private sector market. We consider a set of profit sharing mechanisms and demonstrate that a convex combination of a subset of the mechanisms assures financial incentive for all participants. Finally, we demonstrate the formulations and price sharing mechanism for the aforementioned hexavalent vaccine in the context of the contemporary United States pediatric vaccine market.

Surveillance and genetic characterization of rotavirus strains circulating in four states of North Indian children

Acute gastroenteritis due to Rotavirus (RV) infection is a major cause of morbidity and mortality in infants and young children worldwide. In India, around 0.1 million death reported annually due to RV illness. So, to assess the disease burden continuous surveillance of the circulating genotypes is needed. This study aimed to ascertain the genetic variance of 429 rotavirus positive specimens observed during the period October 2013–September 2014 at four study centers from North India. Out of 1057 patients enrolled, 1018 stool samples were collected at four centers in four different states of North India. Children aged <5 years who showed the symptoms of severe diarrhea and needed hospitalization were enrolled. The stool samples collected were screened by Enzyme Immuno Assay (EIA), and the RV positive samples were characterized by semi-nested PCR. During the study period October 2013 through September 2014, ~42% patients were found to be rotavirus positive of 1018 collected specimen. In Delhi, Rohtak and Meerut, we observed that Rotavirus is seasonal compared to Tanda (HP). The rate of rotavirus detection was significantly higher among children aged below 2 years, and a total of 21.5% of rotavirus infections comprised children aged <6 months. Genotype G1(48.0%) was predominant and frequently circulating strain whereas G12 (16.8%) and G9 (10.0%) was second and third prevalent strain in the four states of North India. High frequency of G1 genotypes was detected under the age group of 6–11 months which is followed by G12, similarly high rate severe disease was observed due to G1 genotypes followed by P[8], P[6] and G12. The most common types of strains were G1P[8] (27.73% of strains), G12P[6] (13.28%), G9P[4] (7.23%) and G1P[6] (6.75%). The rare strain reported were G1P[9]; P[11] strain was detected in combination with G1, G2, and G12. These data emphasized G12 is the second most predominant strain circulating among Northern Indian children highlights the needs for inclusion in the future polyvalent vaccine to break the burden of rotavirus infection.

Polyvalent vaccines: High-maintenance heroes.

Vaccines are the most efficient tools to battle infectious diseases, with an estimated prevention of 2–3 million deaths per year [1]. Vaccine development, however, is costly and challenging, especially when the target pathogen can be subdivided into serologically distinguishable types (serotypes) that individually cause disease. Broad protection against serotypes can be achieved with either polyvalent vaccines of mixed serotype-specific immunogens or by discovery and use of a good immunogen conserved among serotypes. The latter is preferable but technically elusive. The poliovirus vaccine (containing three poliovirus serotypes) was first used as a polyvalent vaccine, beginning with the establishment of the Global Polio Eradication Initiative in 1988, reducing poliomyelitis by 99% [2]. Polyvalency has been arguably more useful than using conserved immunogens to target multiple serotypes, and polyvalency has steadily advanced despite complexity and barriers to manufacturing. Here, we review challenges and developments in polyvalent vaccines.

Implanted ports in adults with primary immunodeficiency.

We sought to learn more about the utility and safety of implanted ports for monthly immunoglobulin G infusions in adults with primary immune deficiency. We reviewed charts of adults who were referred to a single practice during the interval 2006-2016 for evaluation and management of frequent or severe upper and lower respiratory tract and other infections, subnormal total immunoglobulin G or immunoglobulin G subclasses, and suboptimal responses to polyvalent pneumococcal polysaccharide vaccinations; were diagnosed to have primary immune deficiency; and were advised to undergo immunoglobulin G therapy. Of 606 patients, 20 (19 women, 1 man; 16 immunoglobulin G subclass deficiency, 4 common variable immunodeficiency; 3.3%) needed implanted ports because they had inadequate upper extremity superficial venous access. Median age at diagnosis was 48 years (range: 32-65 years). In total, 17 of the 20 patients preferred monthly in-office intravenous immunoglobulin G treatment to weekly at-home subcutaneous immunoglobulin G. The other three patients could not be treated with subcutaneous immunoglobulin G (unfavorable self-treatment experiences and insurance limitations). Median duration of treatment via implanted ports was 73 months (range: 10-153 months). In the man, the first implanted port was replaced after 26 months due to catheter fracture of unknown cause. His second port has been used for 112 months. We observed no other port-related failure, infections, thrombosis, or other adverse events. The utility and safety of implanted ports in adults with primary immune deficiency for whom subcutaneous immunoglobulin G therapy is not desired or feasible are probably similar to those of ports in patients without primary immune deficiency.

Efficacy of a high-potency multivalent foot-and-mouth disease virus vaccine in cattle against heterologous challenge with a field virus from the emerging A/ASIA/G-VII lineage

In 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East were discovered to be caused by a viral lineage (A/ASIA/G-VII), which has recently emerged from the Indian sub-continent. In vitro vaccine matching data generated by the World Reference Laboratory (WRLFMD) indicated that A/ASIA/G-VII field viruses were poorly matched with vaccines (A-SAU-95, A22 IRQ and A-IRN-05) that are already used in the region. In order to assess the likely performance of one of these commercially available FMD vaccines, sixteen cattle were vaccinated with a polyvalent vaccine which contained two serotype A components (A-SAU-95 and A-IRN-05) with a homologous potency of at least 6PD50, and two cattle were left unvaccinated as controls. Twenty-one days later, all 18 cattle were challenged by tongue inoculation with an FMDV field isolate A/IRN/22/2015 from the A/ASIA/G-VII lineage, in line with the European Pharmacopeia PPG test conditions. The two control animals developed generalised FMD, and 7/16 vaccinated animals developed at least one foot lesion, thus only 56.3% were defined as protected. For the vaccine components, there was a significant increase in the probability of protection with increasing serological titres for A-SAU-95 (p = 0.03), but not for A-IRN-05 (p = 0.42). Analysis of FMDV in blood and nasal swabs suggested that vaccination reduced shedding and potential onward spread of FMD virus even if the animal developed foot lesions. In summary, the results from this study suggest that whilst this vaccine would not be appropriate for use in an emergency situation (in previously FMD-free countries), it may be partially effective in the field in endemic countries where repeat prophylactic vaccination is practiced. For emergency reactive vaccination, the findings from this study support the idea that a new vaccine strain should be developed that is tailored to the A/ASIA/G-VII lineage.

Six genes of ompA family shuffling for development of polyvalent vaccines against Vibrio alginolyticus and Edwardsiella tarda

Polyvalent vaccines against more than one species of pathogens are especially important due to the complex ecosystem in aquaculture. We have previously shown that the development of polyvalent vaccines by shuffling six ompA genes from different bacteria with V. parahaemolyticus VP0764 primers. Here, we used the same 6 genes, V. alginolyticus VA0764 and VA1186, V. parahaemolyticus VP0764 and VP1186, E. tarda ompA and E. coli ompA, but with E. tarda ompA primers to develop new polyvalent vaccines. By this approach, we identified 7 potential polyvalent vaccines that were effective against both V. alginolyticus and E. tarda infections. Furthermore, the innate immunity triggered by the vaccines were also explored in three groups, no protection (group I), protection against V. alginolyticus (group II), and protection against both V. alginolyticus and E. tarda (group III). The transcription of IL-1β, IL-6, IL-8, C3b and NF-kB were significantly increased in group II and group III but not group I, where the expression level of group III was higher than group II. In addition, differential activities of succinate dehydrogenase were detected among the three groups. These results indicate the expansion of polyvalent vaccine reservoir with the same shuffling genes but different primers, and promote the understanding of the mechanisms of polyvalent vaccines based on vaccine-induced innate immunity.

Bacteriological cure rate and changes in milk composition in mastitis vaccinated ewes affected with subclinical mastitis.

Aim:The aim of this study was to investigate the effects of using a commercially-available polyvalent mastitis vaccine on the bacteriological cure rate of existing subclinical mastitis in Awassi sheep.Materials and Methods:A total of 164 lactating ewes were divided into two main groups according to udder health and milk somatic cell count (SCC): Group 1=normal (N; n=80) and Group 2=subclinical mastitis (SC; n=84). Each group was then subdivided randomly into two treatment groups: N vaccinated (Nvax; n=38), N non-vaccinated (Nnvax; n=42), SC vaccinated (SCvax; n=42), and SC non-vaccinated (SCnvax; n=42). The vaccine was administered as per manufacturer’s recommendations. Milk samples were collected aseptically from all ewes before vaccine administration (T0) and again on days 28 (T2) and 42 (T3) of the experiment.Results:In the SC group, the bacteriological cure rates in vaccinated and non-vaccinated ewes were 76% and 69%, respectively. In N group, the new intramammary infection rates in vaccinated and non-vaccinated ewes were 48% and 50%, respectively. Vaccination of normal ewes resulted in a significant (p<0.05) reduction in bacterial growth rate both at day 28 and day 42 of the study. The prevalence of new intramammary infection rate in Nvax ewes on days 28 and 42 was 19% and 20%, respectively. The prevalence of new intramammary infection rate in Nnvax group on days 28 and 42 was 33% and 30%, respectively. In SCvax group, the bacterial growth rate on days 28 and 42 was 44% and 35%, respectively. In SCnvax group, the bacterial growth rate on days 28 and 42 was 27% and 32%, respectively. There was no statistically significant effect of vaccination on any of the studied milk composition parameters.Conclusions:This is a preliminary study that indicated a possible protective effect of vaccination against mastitis in sheep. Further, case-controlled studies are indicated to estimate the level of immunity this vaccine provides to vaccinated sheep.

The cost-effectiveness of alternative vaccination strategies for polyvalent meningococcal vaccines in Burkina Faso: A transmission dynamic modeling study.

BackgroundThe introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso.Methods and findingsWe developed and calibrated a mathematical model of meningococcal transmission to project the disability-adjusted life years (DALYs) averted and costs associated with the current Base policy (serogroup A conjugate vaccination at 9 months, as part of the Expanded Program on Immunization [EPI], plus district-specific reactive vaccination campaigns using polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks) and three alternative policies: (1) Base Prime: novel polyvalent meningococcal conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide catch-up campaign for 1–18-year-olds; and (3) Prevention 2: Prevention 1, except the nationwide campaign includes individuals up to 29 years old.Over a 30-year simulation period, Prevention 2 would avert 78% of the meningococcal cases (95% prediction interval: 63%–90%) expected under the Base policy if serogroup A is not replaced by remaining serogroups after elimination, and would avert 87% (77%–93%) of meningococcal cases if complete strain replacement occurs. Compared to the Base policy and at the PMC vaccine price of US$4 per dose, strategies that use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be cost saving if strain replacement occurs, and would cost US$51 (−US$236, US$490), US$188 (−US$97, US$626), and US$246 (−US$53, US$703) per DALY averted, respectively, if strain replacement does not occur.An important potential limitation of our study is the simplifying assumption that all circulating meningococcal serogroups can be aggregated into a single group; while this assumption is critical for model tractability, it would compromise the insights derived from our model if the effectiveness of the vaccine differs markedly between serogroups or if there are complex between-serogroup interactions that influence the frequency and magnitude of future meningitis epidemics.ConclusionsOur results suggest that a vaccination strategy that includes a catch-up nationwide immunization campaign in young adults with a PMC vaccine and the addition of this new vaccine into EPI is cost-effective and would avert a substantial portion of meningococcal cases expected under the current World Health Organization–recommended strategy of reactive vaccination. This analysis is limited to Burkina Faso and assumes that polyvalent vaccines offer equal protection against all meningococcal serogroups; further studies are needed to evaluate the robustness of this assumption and applicability for other countries in the meningitis belt.

Regional, age and respiratory-secretion-specific prevalence of respiratory viruses associated with asthma exacerbation: a literature review.

Despite increased understanding of how viral infection is involved in asthma exacerbations, it is less clear which viruses are involved and to what extent they contribute to asthma exacerbations. Here, we sought to determine the prevalence of different respiratory viruses during asthma exacerbations. Systematic computerized searches of the literature up to June 2017 without language limitation were performed. The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations. We also examined the prevalence of viral infection stratified by age, geographic region, type of respiratory secretion, and detection method. Sixty articles were included in the final analysis. During asthma exacerbations, the mean prevalence of AdV, BoV, CoV, CMV, EnV, HSV, IfV, MpV, PiV, RV and RSV was 3.8%, 6.9%, 8.4%, 7.2%, 10.1%, 12.3%, 10.0%, 5.3%, 5.6%, 42.1% and 13.6%, respectively. EnV, MPV, RV and RSV were more prevalent in children, whereas AdV, BoV, CoV, IfV and PiV were more frequently present in adults. RV was the major virus detected globally, except in Africa. RV could be detected in both the upper and lower airway. Polymerase chain reaction was the most sensitive method for detecting viral infection. Our findings indicate the need to develop prophylactic polyvalent or polyvirus (including RV, EnV, IfV and RSV) vaccines that produce herd immunity and reduce the healthcare burden associated with virus-induced asthma exacerbations.Electronic supplementary materialThe online version of this article (10.1007/s00705-017-3700-y) contains supplementary material, which is available to authorized users.

Immunogenic and Protective Properties of Neisseria meningitidis IgA1 Protease and of Its Truncated Fragments

Four recombinant proteins, MA28–P1004LEH6, ME135–H328LEH6, MW329–H622LEH6 and MH835–P1004LEH6, were prepared based on the genomic sequence of IgA1 protease from Neisseria meningitidis serogroup B strain H44/76. The immunogenic and protective properties of these proteins were studied in a mouse model. The predicted T- and B-epitopes located in the N-terminal part of amino acid sequence of this enzyme are very important for the formation of effective protection against meningococci of the three main epidemic serogroups A, B, and C. The small-sized recombinant protein having the sequence ME135–H328LEH6 (molecular weight 23367 Da) appears to be as protective against meningococci of the tested serogroups as the high molecular MA28–P1004LEH6 (molecular weight 109019 Da), the latter being a large-sized analog of full-length IgA1 protease. These proteins can be promising candidates for a polyvalent meningococcal vaccine.

Quantitative Proteomic Profiling Reveals Novel Plasmodium falciparum Surface Antigens and Possible Vaccine Candidates

Despite recent efforts toward control and elimination, malaria remains a major public health problem worldwide. Plasmodium falciparum resistance against artemisinin, used in front line combination drugs, is on the rise, and the only approved vaccine shows limited efficacy. Combinations of novel and tailored drug and vaccine interventions are required to maintain the momentum of the current malaria elimination program. Current evidence suggests that strain-transcendent protection against malaria infection can be achieved using whole organism vaccination or with a polyvalent vaccine covering multiple antigens or epitopes. These approaches have been successfully applied to the human-infective sporozoite stage. Both systemic and tissue-specific pathology during infection with the human malaria parasite P. falciparum is caused by asexual blood stages. Tissue tropism and vascular sequestration are the result of specific binding interactions between antigens on the parasite-infected red blood cell (pRBC) surface and endothelial receptors. The major surface antigen and parasite ligand binding to endothelial receptors, PfEMP1 is encoded by about 60 variants per genome and shows high sequence diversity across strains. Apart from PfEMP1 and three additional variant surface antigen families RIFIN, STEVOR, and SURFIN, systematic analysis of the infected red blood cell surface is lacking. Here we present the most comprehensive proteomic investigation of the parasitized red blood cell surface so far. Apart from the known variant surface antigens, we identified a set of putative single copy surface antigens with low sequence diversity, several of which are validated in a series of complementary experiments. Further functional and immunological investigation is underway to test these novel P. falciparum blood stage proteins as possible vaccine candidates.

Construction, immune protection and innate immune response of shuffled polyvalent ompAs vaccines

Our previous studies demonstrated that molecular breeding via DNA shuffling directs the evolution of polyvalent vaccines with desired traits, which leads to generation of polyvalent ompA vaccines using Vibrio alginolyticus VA0764 primers. Here, we replaced VA0764 primers with Edwardsiella tarda ompA primers to generate new polyvalent ompA vaccines by DNA shuffling of the same five ompA genes from four species of bacteria E. tarda, V. parahaemolyticus, V. alginolyticus and Escherichia coli. We identified four polyvalent vaccine candidates from a eukaryotic expressing library EompAs-FE containing 82 ompAs using active immune protection against V. alginolyticus and E. tarda. Furthermore, we explored mechanisms of polyvalent vaccine candidates by investigation of the innate immune response to these ompAs, and found that expression of IL-1β, IL-8, IL-15, COX-2, IFN-γ, TLR-1, TLR-3 and C3b genes was elevated as a characteristic feature of these polyvalent vaccine candidates. These results indicate that use of different primers to construct a DNA library selects new evolution of polyvalent vaccines with desired traits, and polyvalent ompA vaccines elicit high innate immune response.