Even if serum antibodies are important for protection against whooping cough, their levels decline rapidly after vaccination, while protection against severe disease lasts longer [12]. Several

studies have demonstrated that cell-mediated immune mechanisms involving individual T and B cell Wnt inhibitor review populations are implicated as well [12], [13] and [14]. The contribution of T cells to protection was demonstrated in animal models [15], [16], [17], [18], [19], [20] and [21], and the appearance of B. pertussis (Bp)-specific T lymphocytes soon after infection or vaccination is well recognized [22], [23], [24] and [25], as well as the importance for protection of both magnitude and quality of the immune responses [26]. Therefore, in the context of the current re-emergence of pertussis in countries with high vaccination coverage, exploring in detail the long-term Crizotinib T cell responses induced by vaccination may be of interest. Because several years after vaccination the frequency of circulating antigen-specific cells is low, we have developed

a sensitive technique that allows expansion of the responsive population. We then examined the T cell responses in a cohort of 9- to 12-year-old children, vaccinated in their infancy with either wP- or aP-vaccines. Blood samples were collected from seven healthy adults who had been vaccinated with Boostrix 1–14 months before for the optimization of the technique, and from 23 children with a median age of 10.1 years (range 9.0–12.1). As a consequence of changes in the Belgian vaccination recommendations, 11 children received the wP vaccines Tetracoq (Sanofi Pasteur, Lyon, France) or Combivax (GlaxoSmithKline, Rixensart, Belgium) whereas the aP vaccine Tetravac (Sanofi

Pasteur) was given to 12 children. The median age at which each of the doses was administered, was 3.23 (dose 1), 4.57 (dose 2), 5.57 (dose 3) and 14.3 months (dose 4) respectively. All children received an aP booster vaccine (Tetravac or Infanrix-IPV from GlaxoSmithKline) between 5.5 and 8.2 years Levetiracetam of age, and the median time elapsed between the booster and this study was 4 years (range 1.8–5.5 years). There was a significant difference between the time after the last booster vaccine for wP compared to aP vaccinated children (median = 4.8 year for wP- versus 2.7 year for aP-vaccinated children; p = 0.004). The ethical committees of Hôpital Erasme and Universitair Ziekenhuis Brussel (Brussels, Belgium) approved the study and participants or their parents signed the informed consent forms. Tetravac, the aP vaccine used for infant vaccination in this study, contains 2 Bp antigens, filamentous hemagglutinin (FHA) and pertussis toxin (PT). These antigens were therefore selected for the cellular immune assays.

The substantially lower attack rates in seropositives are an important consideration that should not be ignored in these discussions. Therapeutic efficacy of the vaccines was not specifically evaluated in the end of study publications, in large measure because there was no evidence for it in interim analyses. Although the clinical trials were primarily designed to evaluate immunoprophylaxis, the fact that women who had prevalent cervicovaginal infection or low grade disease were not excluded at entry provided a cohort to evaluate therapeutic efficacy. In the CVT, time to clearance

of prevalent infection was evaluated. There was no difference in the rate of clearance of vaccine or non-vaccine mTOR inhibitor Epigenetics inhibitor types in Cervarix® vaccinees and control [37]. For example, 48.9% and 49.8% of HPV16/18 infections were cleared after 12 months in vaccine recipients and controls, respectively. The therapeutic activity of Gardasil® was evaluated in FUTURE II [15]. No significant difference in the rate of progression of HPV16/18 infection to CIN2+ was observed in VLP vaccinees versus controls,

11.1% and 11.9%, respectively. Thus the VLP vaccines do not appear to alter the course of established cervicovaginal HPV infection or disease. Both vaccines exhibited excellent safety profiles in the clinical trials. Mild to moderate injection-site symptoms, headache and fatigue were the most common adverse events in Cervarix® and Gardasil® vaccinees and controls. Injection-site pain ranged from 83.0–93.4%

in vaccine groups and from 75.5–87.25% in control groups [14], [15], [38] and [39]. Headache and fatigue was reported in 50-60% of participants in both groups. These solicited symptoms were transient and resolved spontaneously and did not increase with number of doses. Symptoms were not notably different in women with evidence of prevalent or past infection [32] and [35]. In a randomized control trial directly comparing the two vaccines, injection-site pain was somewhat higher with Cervarix® than with Gardasil®; 92.9% (95% CI: 90.4–95.0) and 71.6% (95% first CI: 67.5–75.4) respectively [40]. Grade 3 severity was reported in 17.4% (95% CI: 14.2–20.9) and 3.4% (95% CI: 2.0–5.4) in Cervarix® and Gardasil® groups respectively. However, compliance rates with the three-dose schedule were similarly high (>84%). The inclusion of the immune stimulating component MPL in the Cervarix® adjuvant might account for somewhat higher reactogenicity of the vaccine [38]. For both Cervarix® and Gardasil®, vaccine and control groups experienced similar rates of serious adverse events (SAEs) (Table 8). The numbers of SAEs judged to be possibly related to vaccine injection was low for both vaccines and similar to the numbers in the control groups (Table 8). Pregnancy outcomes have received special attention, given the target ages of catch up vaccination programs.

Furthermore, more pathogenic viruses such as the newly emerged pandemic H1N1 virus of 2009 (pH1N1/09)

for which among others, relatively young people were at an increased risk, highlight the need for improved influenza vaccines that induce better, more cross-protective, and longer lasting immunity than the current seasonal vaccines do. Vaccines administered parenterally induce effective systemic immune responses, but only limited local immunity in the respiratory tract. Locally produced buy Protease Inhibitor Library specific antibodies, in particular secretory IgA (S-IgA) can provide immunity via their unique capability to neutralize a pathogen before it even passes the mucosal barrier [4] and [5]. Moreover S-IgA antibodies have been demonstrated to contribute to the establishment of increased cross-protection from influenza [6]. Nasal administration of vaccine has the potential of establishing mucosal immune responses at the first site of natural infection [7]. In addition, nasal administration using a needle free delivery system is non-invasive, simply

accessible and painless. The currently licensed nasally administered influenza vaccines are live attenuated influenza vaccines selleck compound (LAIV). The LAIV vaccine manufactured by Medimmune, sold under the trade name FluMist in the US and Fluenz in Europe, has proven to be effective against seasonal infection and to provide better cross-protection against drifted influenza virus strains than the non-live seasonal vaccines [8], [9] and [10]. However, the use of LAIV is currently restricted to the age group of 2 to 59 years, thus excluding

children below age 2 as well as the elderly, both populations classified as major high risk groups by the WHO [2]. Therefore, nasal administration of an inactivated influenza vaccine that would be safe and protective through systemic and mucosal immunity, would be an attractive alternative to currently used influenza vaccines. Appropriate Adenylyl cyclase adjuvants or carrier systems have shown to be indispensable to ensure effective stimulation of the mucosal immune system when non-replicating split or subunit antigens were used [11]. A mucosal adjuvant would ideally increase the uptake of the antigen through the mucus and mucous membrane and reduce the required antigen dose while eliciting mucosal as well as systemic immunity. Moreover, the adjuvant should ideally not cause adverse side effects. Concerns about the safety of mucosal adjuvants are real, since the reporting of an increased incidence of Bell’s palsy syndrome seen after using an intranasally administered inactivated influenza vaccine, adjuvanted with an apparently insufficiently detoxified mutant of the E. coli heat labile enterotoxin [12] and [13]. Nevertheless, research on the design and development of effective and safe intranasal adjuvants is ongoing and several mucosal adjuvants which support influenza immunity are currently under investigation [14], [15], [16], [17] and [18].

The electropherograms obtained were analyzed using the sequencing analysis software (Sequence Navigator, version 1.01, Applied Biosystems). The nt and deduced aa sequences were compared with sequences available in the NCBI (National Center for Biotechnology Information) GenBank database using the BLAST (Basic Local Alignment Search Tool) program. Phylogenetic and molecular Autophagy activator evolutionary analyses were conducted using MEGA version 4.0 [36]. Dendrograms constructed were confirmed by two different methods,

neighbor joining and maximum parsimony. The data were analyzed using Epi Info 2002 and Stata 10.0. Chi square and Mann Whitney U tests were performed to determine the significance of differences observed between groups. Partial nucleotide Bioactive Compound Library chemical structure sequences of VP1, VP2, VP3, VP4, VP6, VP7, NSP1, NSP2, NSP3, NSP4 and NSP5 of the G10P[15] strains were submitted to the GenBank database and their accession numbers are HQ660637, HQ660638, HQ660639, FJ798615, FJ798616, FJ798617, HQ660640, HQ660641, HQ660642, FJ798618, HQ660643 respectively. The median (interquartile range [IQR]) age of the 394 children enrolled in the study was 10 (7) months, with >90% of children less than 2 years of age. The median Vesikari score of diarrheal severity was 11.0 and the children required

admission for a mean duration of 2.8 days. Of 394 children screened, we found that 158 children were infected with rotavirus (40%). The common G types identified in order of frequency were G1 (47/158, 29.7%), G2 (43/158, 27.2%), G9 (22/158, 13.9%), G10 (2/158, 1.2%), G12 (1/158, 0.6%) and mixed infections (27/158, 17.8%). The common P types were P[4] accounting for 57/158 (36%) samples, P[8] 57/158 (36%), P[11] 3/158 (1.8%) and P[6] 2/158 (1.2%). Mixed infections with varied P types were seen in 5 (3.2%). G typing alone was possible in 23 samples Olopatadine (14.4%), only P typing in 5 samples (3.6%) and 11 samples were completely untypeable (6.9%). The common G:P combinations seen

in children were, G2P[4] in 39/158 (24.6%) samples, G1P[8] in 29/158 (18.3%) samples, G9P[8] in 21/158 (13.2%) samples, G1P[4] in 4/158 (2.5%) samples and G10P[11] in 1/158 sample (0.6%) (Fig. 1a). We collected total of 627 samples from animals with diarrhea, including 589 cows (25 were calves), 2 buffaloes, 11 bullocks and 25 goats (11 were kids). The mean duration of diarrhea was 4.5 days for adult animals, 4 days for calves and 3 days for goat kids. Out of 627 animals we found 35 (1 bullock, 2 goats, 32 cows) infected with rotavirus (5.5%). The common G types identified in order of frequency were G6 (17/35, 48.5%), G2 (10/35, 28%), G10 (4/35, 11%), G8 (2/35, 5.7%) and mixed infections (2/35, 5.7%).

The full MERS-CoV genome isolated from a Qatari dromedary camel is highly similar to the human England/Qatar 1 virus isolated in 2012 and has efficiently been replicated in human cells using human DPP4 as entry receptor, providing further evidence for the

zoonotic potential of dromedary MERS-CoV [10]. Although, we cannot conclude whether the people were infected by camels or vice versa or if yet another source was responsible, increasing evidence indicates that camels Epigenetics inhibitor represent an important link in human infections with MERS-CoV. Intensive vaccine control and risk-reduction targeting dromedary camels might be effective in eliminating the virus from the human population. The coronavirus spike protein (S) is a class I fusion protein. Cellular entry of the virus has been demonstrated to be mediated by the S protein through the receptor binding domain (RBD) in the N-terminal subunit (S1) and the fusion peptide in the C-terminal subunit (S2) [11] and [12]. For betacoronaviruses, the S protein has been shown to be the main antigenic component responsible for inducing high titers of neutralizing antibodies and/or protective immunity against

infection in patients who had recovered from SARS [13] and [14] and response levels correlated well with disease outcomes [15] and [16]. The S protein has therefore been selected as an important target for vaccine development [17], [18], [19], [20] and [21]. Recent work shows that modified vaccinia virus Compound Library chemical structure Ankara expressing the S protein of MERS-CoV elicits high titers of S-specific neutralizing antibodies in mice [22]. Adenovirus 5 (Ad5)-vectored

candidate vaccines induce potent and protective immune responses against several pathogens in humans and a variety of animals [18], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32] and [33]. Although a trial of a candidate DNA/rAd5 HIV-1 preventive vaccine showed lack of efficacy [37] and the high prevalence of pre-existing anti-Ad5 immunity may have been a major limitation [38] in humans, replication-defective adenovirus vaccines are among the most attractive vectors for veterinary vaccine development, given the relative speed and low cost of development and production. Most adenoviruses infect their host through the airway epithelium and replicate in the mucosal tissues of the because respiratory tracts [39]. Because of their ability of to elicit mucosal immune responses, adenoviruses could be an attractive vector for inducing MERS-CoV-specific immunity in dromedary camels, the putative animal reservoir. Interestingly, sera antibodies against adenovirus type 3 were detected in 1.3% of dromedaries in Nigeria [34] and in 43 of 120 camels in Egypt [35]. The occurrence of adenovirus type 3 respiratory infections in camels was studied in Sudan and a 90% seroprevalence was detected [36]. Here, we describe the development of recombinant type 5 adenoviral vector expressing, codon-optimized MERS-S and MERS-S1 (Ad5.

CD4+ T-cells secrete IFN-γ selleck compound and drive B-cell maturation. Th17 cells play a role in host defense against extracellular pathogens by mediating the

recruitment of neutrophils and macrophages to infected tissues [25] and [26]. The female reproductive tract restricts entry of activated T-cells in the absence of inflammation or infection [27]. Consequently, parenteral vaccines that rely on cellular immunity to prevent STIs have not been successful. Recently, vaccines that elicit tissue-resident memory T-cell responses have been shown to be feasible [28] and [29] and may hold the key to a successful vaccination strategy against herpes simplex viruses and other sexually transmitted pathogens. In the male reproductive tract, keratinized stratified squamous epithelial cells cover the external surface of the penis. The male urethral orifice consists

of a non-keratinized stratified squamous epithelium that transitions in the penile shaft to a pseudostratified columnar epithelium. The urethral epithelium expresses several membrane-associated mucins that act as a first-line of defense [30]. The male reproductive tract is an immune privileged site. For example, tight junctions between Sertoli cells prevent entry of complement and immunoglobulins into the seminiferous tubules. This is referred to as the blood–testis barrier. This relative suppression of adaptive immunity is accompanied by an enhanced innate immune response against local infections. Far less is known about the mucosal immune system of the male

reproductive tract than is Romidepsin purchase known about the female tract. Antimicrobial peptides are found in the testes, seminal vesicles, epididymis, and prostate [31]. As with the female reproductive tract, epithelial cells lining the male urethral tract express PRRs and are involved in antigen presentation [32]. Macrophages and dendritic cells are abundant in the prepuce and penile urethra and are found in the epididymis and prostate [33]. They are notably absent in the seminal vesicles. Neutrophils are present in the prepuce and variably present in the urethra, prostate, and epididymis. NK cells have been demonstrated in the prostate, testis, and prepuce. IgG is the main immunoglobulin found in seminal Astemizole plasma and it is serum-derived. IgA, mainly IgA1, is also present and is derived from serum and in situ production. B-cells that produce these antibodies are mainly found in the penile urethra and prostate. CD8+ T-cells and CD4+ T-cells are abundant in the penile urethra and also found in the vas deferens, epididymis, seminiferous tubules, and prepuce. It appears that the penile urethra, with the abundant distribution of immune cells, may be a major site of immune induction [32]. Microbiota” represent an assemblage of microorganisms present in a defined environment. The overwhelming majority of microbial species (>99%) resist cultivation in the laboratory [34] and [35].

The adjuvant effect of including CaP in PCMCs was confirmed for both antigens ( Table 1). This was particularly marked for the anti-CyaA* response as only one mouse in the 0% CaP group produced a detectable anti-CyaA* IgG titre at each time point investigated. Increasing the CaP content did not significantly further increase the antigen-specific IgG titres or alter the duration of antibody response. The attempted prime-boost Selleckchem Epacadostat formulation failed to enhance immunogenicity compared to other CaP PCMC formulations. J774.2 cells were incubated with equal amounts of either soluble BSA-FITC or BSA-FITC formulated

as 0% or 8% CaP PCMCs. Uptake of fluorescent antigen was visualised by confocal laser-scanning microscopy (Fig. 5, panels A–C) and quantified by flow cytometry (panels D–F). Confocal microscopy showed that soluble BSA-FITC was poorly phagocytosed, with J774.2 cells containing low levels of fluorescence (Fig. 5A). In contrast, loading BSA-FITC onto PCMCs increased phagocytosis, with cells displaying punctate regions of green fluorescence (Fig. 5B) and this was further enhanced with CaP PCMCs (Fig. 5C). These observations were confirmed by flow cytometry. The P2 daughter population was derived

from the parent population P1. The increase in MFI of the P2-gated population of the cells upon exposure Alectinib manufacturer to BSA-FITC PCMCs (Fig. 5E) and the further increase in the presence of CaP-modified PCMCs (Fig. 5F) indicates a greater phagocytosis of these particles compared to soluble BSA-FITC (Fig. 5D). These results, in combination with published data, demonstrate that PCMC formulations are suitable for vaccine applications and may address problems associated with current vaccines. Moreover, CaP PCMCs were shown to be immunogenic and to promote a more

Dichloromethane dehalogenase mixed Th1/Th2 response in comparison to traditional formulations and to soluble PCMCs [5] and [7]. Modification of the surface of PCMC with an outer layer of CaP altered the particle morphology from planar discs to rod-like structures and significantly decreased the rate of antigen release in vitro. PCMCs without CaP released antigen almost immediately in aqueous buffers whereas increasing the CaP loading progressively decreased the rate of antigen release. This is consistent with release being controlled by dissolution of an outer layer of CaP, the thickness of which is expected to increase with CaP loading. This suggests that CaP PCMCs would potentially show enhanced immunogenicity due to a depot effect in vivo as has been proposed for other adjuvants [2] and [15]. Surprisingly, mice immunised with DT formulated into soluble PCMCs showed enhanced immunogenicity compared to soluble DT antigen. The in vitro solubility data indicated that this enhanced immunogenicity was not due to a depot effect.

Implementing separate vertical programs would be a waste if the same infrastructure could be used to deliver multiple interventions. Promoting delays in sexual debut, fewer sexual partners and condom use go hand in hand and could be part of delivering STI vaccines to adolescents and young adults. Epidemiologically, preventing STI infection in one individual prevents infections in those they would Venetoclax chemical structure otherwise expose. Risks of acquisition and transmission combine to allow the spread of STIs and similarly reducing those risks combines to stop spread. This combination

can be more than additive (i.e. synergistic). This epidemiological synergy is determined by the way reduced risks combine [5], but means that adding multiple partially efficacious interventions can have a big effect. However, these combined impacts only apply when there remains risk and is more likely to apply for those with high risks of acquiring and transmitting infection. In many cases if we have reduced risk with one intervention it will simply be a waste to provide further interventions. Targeting to high risk

groups reduces the potential for such waste as infection is unlikely to be fully controlled by one intervention in these groups. Despite all the uncertainty about the prevalence of infection, the burden of disease, the effectiveness of vaccination and the cost of vaccination, it is possible to gain some insight into how cost effective STI vaccines will be. In the numerator of the cost effectiveness all ratio we need the costs of the selleck vaccination program with the medical care costs or costs of programs no longer required removed; in the denominator we need the health gains achieved by the program. The greater prevalence

of HSV-2 and chlamydia, especially in developed countries makes it more likely that vaccines against these infections would be used across the population. To explore the cost effectiveness of an HSV-2 vaccine in the US the impact of vaccination over 30 years is explored, assuming that an annual cohort is immunized before commencing sexual activity. The results in Fig. 4 show the cost effectiveness for different measures of health lost through the infection, different costs of vaccination and different vaccine coverages. For all but the highest vaccine cost and lowest health gain without infection the vaccine would be deemed cost effective. Evaluation of health states with HSV-2 is limited but one study of patients with recurrent genital herpes found a roughly 10–20% loss of utility, which combined with 10–20% of infections being symptomatic places us in the 1–4% range for loss of utility. Targeting, if feasible, would decrease the costs of the program and make vaccination more cost effective. Because chlamydia is more likely to be symptomatic and has similar medical care costs in the US, a chlamydia vaccine is also likely to be cost effective.

Clinical outcomes revealed that the majority of

these cases were unrecognized multifetal pregnancies, ongoing or vanishing twins, with a small number of triploid pregnancies also detected. The ability to detect vanishing twin pregnancies is clinically important as it will reduce the number of false-positive results and thereby reduce unnecessary invasive diagnostic procedures. Future longitudinal studies, designed to evaluate the typical Stem Cell Compound Library solubility dmso time period for which residual fetal cfDNA from vanishing twins remains detectable, may provide greater insight into appropriate clinical care in these patients. “
“LOX-1 is a lectin-like oxidized LDL receptor (also known as oxidized LDL receptor 1—OLR1), which was initially described in endothelial cells by Sawamura et al. [1]. LOX-1 expression has subsequently been described in both smooth muscle cells and macrophage in atherosclerotic plaques [2] as well as http://www.selleckchem.com/products/Gemcitabine-Hydrochloride(Gemzar).html in other cell types including adipocytes [3], platelets [4], and chondrocytes [5]. LOX-1 expression can be induced or up-regulated by a number of processes many of which are involved in the atherosclerotic process, including hypertension, sepsis, inflammatory mediators, dyslipidemia, advanced

glycation end products, and fluid shear stress (reviewed in Ref. [6]). LOX-1 performs a number of functions in addition to oxidized LDL (oxLDL) binding, such as binding of apoptotic cell bodies and aged red blood cells [7] and acting as a leukocyte adhesion molecule [8]. Binding of oxLDL to LOX-1 induces endothelial dysfunction and apoptosis, stimulating reactive oxygen species (ROS) production and NFκB activation [9], strongly linking LOX-1 with the process of atherosclerosis Dipeptidyl peptidase [6] and [10]. Several studies in hyperlipidemic mice have demonstrated a link between LOX-1 and atherosclerosis. Mehta et al. [11] created a LOX-1−/−/LDLR−/− mouse, which on high-fat diet exhibited reduced plaque development in the aorta compared to controls. In addition, the LOX-1−/−/LDLR−/− mice also

demonstrated a number of anti-atherosclerotic features, e.g., increased IL-10 levels and eNOS activity, with a concomitant reduction in MAPK p38 and NFκB activation. Inoue et al. [12] created a bovine LOX-1 transgenic mouse, where LOX-1 was overexpressed in multiple cell types including vascular and cardiac tissue. Among the pathologies displayed in this transgenic mouse was an increase in ox-LDL uptake and atheroma-like lesions in coronary arteries. In addition, Ishigaki et al. [13] used an adenoviral vector to overexpress LOX-1 in the liver, enhancing hepatic uptake of ox-LDL and reducing atheroma in the aorta. Taken together, these experiments clearly demonstrated a role for LOX-1 in atherosclerosis, although the contribution of endothelial vs. smooth muscle cell or macrophage expression has yet to be determined.

This paper presents an ethical framework for addressing questions concerning placebo-controlled trials, as developed by a recent WHO expert panel. The framework sets out the conditions under which placebo use is clearly acceptable and clearly unacceptable in vaccine trials. It then specifies four situations in which the use of placebo controls may be ethically justified even when an efficacious vaccine exists. In these situations, it is necessary that the study question cannot be answered in an active-controlled trial design; that the risks of delaying or foregoing the efficacious vaccine are adequately

mitigated; that the risks of using a placebo control are justified by the social or public health value of the research; and that the research is

responsive to local health needs. The ultimate judgement about the acceptability of using a placebo control when check details an efficacious vaccine exists will depend on the specifics of the given trial. It is therefore critical that investigators and sponsors develop the design of vaccine trials in close collaboration with host country stakeholders, and that RECs and others thoroughly evaluate study protocols based on the available SB431542 manufacturer evidence and all relevant reasons. It is our hope that these recommendations will help to ensure that participants in vaccine trials are protected from unjustifiable risks, while facilitating the conduct of valuable and urgently needed vaccine research. Annette Rid, Abha Saxena and Peter Smith drafted the initial manuscript based on the WHO meeting report. All authors reviewed and revised the manuscript, and approved the final manuscript as submitted. The WHO Expert Consultation was supported by PATH, a non-profit organization funded by the Bill & Melinda Gates Foundation. Annette Rid received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme

(FP7/2007-2013) under REA grant agreement no. 301816. Peter G. Smith receives support from the MRC and DiFD (MR/K012126/1). Mark Sheehan is grateful for the support of the Oxford NIHR Biomedical Research Centre. Several authors of this paper have been involved in placebo-controlled vaccine trials that were conducted in situations in which a vaccine already existed that was at least partially efficacious against the conditions under found study. Many thanks to John Boslego and David Wendler for comments on a previous version of this manuscript. “
“In contrast to many other vaccines, influenza vaccines are frequently updated to be effective against newly evolving human influenza viruses that are likely to circulate in the following influenza season. WHO convenes technical consultations (vaccine composition meetings (VCM)) twice a year to provide guidance to national public health authorities and vaccine manufacturers on the viruses to be included in trivalent or quadrivalent influenza vaccines for the following influenza seasons in the Northern and Southern Hemispheres.