Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus.

Starvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting normal cells against off-target lysis. Human colorectal carcinoma (CRC) cell lines as well as human normal colon cell lines were subjected to various starvation regimes and infected with MeV-GFP. The applied fasting regimes were either short-term (24 h pre-infection) or long-term (24 h pre- plus 96 h post-infection). Cell-killing features of (i) virotherapy, (ii) starvation, as well as (iii) the combination of both were analyzed by cell viability assays and virus growth curves. Remarkably, while long-term low-serum, standard glucose starvation potentiated the efficacy of MeV-mediated cell killing in CRC cells, it was found to be decreased in normal colon cells. Interestingly, viral replication of MeV-GFP in CRC cells was decreased in long-term-starved cells and increased after short-term low-glucose, low-serum starvation. In conclusion, starvation-based virotherapy has the potential to differentially enhance MeV-mediated oncolysis in the context of CRC cancer patients while protecting normal colon cells from unwanted off-target effects.

Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus.

Oncolytic viruses (OV) constitute highly promising innovative biological anticancer agents. However, like every other antitumoral compound, OV are also faced with both primary and secondary mechanisms of resistance. To overcome those barriers and moreover amplify the therapeutic potential of OV, we evaluated a novel combined approach composed of the oral histone deacetylase inhibitor resminostat and an oncolytic measles vaccine virus (MeV) for a future epi­virotherapy of pancreatic ductal adenocarcinoma. Cytotoxicity assays revealed that combined epi-virotherapeutic treatment of four well-characterized human pancreatic cancer cell lines resulted in a beneficial tumor cell killing as compared to either monotherapeutic approach. Notably, epi-virotherapeutic treatment of MIA PaCa-2 and partly also of PANC­1 pancreatic cancer cells resulted in a tumor cell mass reduction being significantly more pronounced than it would be expected in case of an additive effect only, indicating a synergistic mode of action when combining resminostat with MeV. We further found that the epigenetic compound resminostat neither impaired MeV growth kinetics nor prevented the activation of the interferon signaling pathway which plays an important role in mediating primary and secondary resistances to OV. Moreover, we yielded information that the pharma-codynamic function of resminostat was presumably not altered in the course of pancreatic cancer cell infections with MeV. Taken together, these promising results favor the onset of epi-viro-thera-peutic clinical trials in patients suffering from advanced pancreatic ductal adenocarcinoma.

Measles Edmonston vaccine strain derivatives have potent oncolytic activity against osteosarcoma.

Osteosarcoma (OS) is the most common primary bone tumor affecting children and young adults, and development of metastatic disease is associated with poor prognosis. The purpose of this study was to evaluate the antitumor efficacy of virotherapy with engineered measles virus (MV) vaccine strains in the treatment of OS. Cell lines derived from pediatric patients with OS (HOS, MG63, 143B, KHOS-312H, U2-OS and SJSA1) were infected with MV expressing green fluorescent protein (MV-GFP) and MV-expressing sodium iodide symporter (MV-NIS) strains. Viral gene expression and cytotoxicity as defined by syncytial formation, cell death and eradication of cell monolayers were demonstrated. Findings were correlated with in vivo efficacy in subcutaneous, orthotopic (tibial bone) and lung metastatic OS xenografts treated with the MV derivative MV-NIS via the intratumoral or intravenous route. Following treatment, we observed decrease in tumor growth of subcutaneous xenografts (P=0.0374) and prolongation of survival in mice with orthotopic (P<0.0001) and pulmonary metastatic OS tumors (P=0.0207). Expression of the NIS transgene in MV-NIS infected tumors allowed for single photon emission computed tomography and positron emission tomography-computed tomography imaging of virus infected tumors in vivo. Our data support the translational potential of MV-based virotherapy approaches in the treatment of recurrent and metastatic OS.

A randomized trial of an early measles vaccine at 4½ months of age in Guinea-Bissau: sex-differential immunological effects.

BACKGROUND: After measles vaccine (MV), all-cause mortality is reduced more than can be explained by the prevention of measles, especially in females. OBJECTIVE: We aimed to study the biological mechanisms underlying the observed non-specific and sex-differential effects of MV on mortality. METHODS: Within a large randomised trial of MV at 4.5 months of age blood samples were obtained before and six weeks after randomisation to early MV or no early MV. We measured concentrations of cytokines and soluble receptors from plasma (interleukin-1 receptor agonist (IL-1Ra), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, soluble urokinase-type plasminogen activator receptor), and secreted cytokines (interferon-γ, TNF-α, IL-5, IL-10, IL-13, IL-17) after in vitro challenge with innate agonists and recall antigens. We analysed the effect of MV in multiple imputation regression, overall and stratified by sex. The majority of the infants had previously been enrolled in a randomised trial of neonatal vitamin A. Post hoc we explored the potential effect modification by neonatal vitamin A. RESULTS: Overall, MV versus no MV was associated with higher plasma MCP-1 levels, but the effect was only significant among females. Additionally, MV was associated with increased plasma IL-1Ra. MV had significantly positive effects on plasma IL-1Ra and IL-8 levels in females, but not in males. These effects were strongest in vitamin A supplemented infants. Vitamin A shifted the effect of MV in a pro-inflammatory direction. CONCLUSIONS: In this explorative study we found indications of sex-differential effects of MV on several of the plasma biomarkers investigated; in particular MV increased levels in females, most strongly in vitamin A recipients. The findings support that sex and micronutrient supplementation should be taken into account when analysing vaccine effects. TRIAL REGISTRATION: clinicaltrials.gov number NCT 00168545.

Measles virus vaccine-infected tumor cells induce tumor antigen cross-presentation by human plasmacytoid dendritic cells.

PURPOSE: Plasmacytoid dendritic cells (pDC) are antigen-presenting cells specialized in antiviral response. The measles virus vaccine is proposed as an antitumor agent to target and specifically kill tumor cells without infecting healthy cells. EXPERIMENTAL DESIGN: Here, we investigated, in vitro, the effects of measles virus vaccine-infected tumor cells on the phenotype and functions of human pDC. We studied maturation and tumor antigen cross-presentation by pDC, exposed either to the virus alone, or to measles virus vaccine-infected or UV-irradiated tumor cells. RESULTS: We found that only measles virus vaccine-infected cells induced pDC maturation with a strong production of IFN-α, whereas UV-irradiated tumor cells were unable to activate pDC. This IFN-α production was triggered by the interaction of measles virus vaccine single-stranded RNA (ssRNA) with TLR7. We observed that measles virus vaccine-infected tumor cells were phagocytosed by pDC. Interestingly, we showed cross-presentation of the tumor antigen NYESO-1 to a specific CD8(+) T-cell clone when pDC were cocultured with measles virus vaccine-infected tumor cells, whereas pDC were unable to cross-present NYESO-1 after coculture with UV-irradiated tumor cells. CONCLUSIONS: Altogether, our results suggest that the use of measles virus vaccine in antitumor virotherapy induces immunogenic tumor cell death, allowing pDC to mature, produce high amounts of IFN-α, and cross-present tumor antigen, thus representing a mode of recruiting these antigen-presenting cells in the immune response. Clin Cancer Res; 19(5); 1147-58. ©2012 AACR.

Attenuated oncolytic measles virus strains as cancer therapeutics.

Attenuated measles virus vaccine strains have emerged as a promising oncolytic vector platform, having shown significant anti-tumor activity against a broad range of malignant neoplasms. Measles virus strains derived from the attenuated Edmonston-B (MV-Edm) vaccine lineage have been shown to selectively infect, replicate in and lyse cancer cells while causing minimal cytopathic effect on normal tissues. This review summarizes the preclinical data that led to the rapid clinical translation of oncolytic measles vaccine strains and provides an overview of early clinical data using this oncolytic platform. Furthermore, novel approaches currently under development to further enhance the oncolytic efficacy of MV-Edm strains, including strategies to circumvent immunity or modulate immune system responses, combinatorial approaches with standard treatment modalities, virus retargeting as well as strategies for in vivo monitoring of viral replication are discussed.

A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer.

Breast cancer is the most common malignancy and the second leading cause of female cancer mortality in the United States. There is an urgent need for development of novel therapeutic approaches. In this study, we investigated the antitumor potential of a novel viral agent, an attenuated strain of measles virus deriving from the Edmonston vaccine lineage, genetically engineered to produce carcinoembryonic antigen (CEA) against breast cancer. CEA production as the virus replicates can serve as a marker of viral gene expression. Infection of a variety of breast cancer cell lines including MDA-MB-231, MCF7 and SkBr3 at different multiplicities of infection (MOIs) from 0.1 to 10 resulted in significant cytopathic effect consisting of extensive syncytia formation and massive cell death at 72-96 h from infection. All breast cancer lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production. TUNEL assays indicated an apoptotic mechanism of syncytial death. The efficacy of this approach in vivo was examined in a subcutaneous Balb C/nude mouse model of MDA-MB-231 cells. Intravenous administration of MV-CEA at a total dose of 1.2 x 10(7) TCID50 resulted in statistically significant tumor growth delay ( p=0.005) and prolongation of survival ( p=0.001). In summary, MV-CEA has potent antitumor activity against breast cancer lines and xenografts. Monitoring marker peptide levels in the serum could serve as a low-risk method of detecting viral gene expression during treatment and could allow dose optimization and individualization of treatment. Trackable measles virus derivatives merit further exploration in breast cancer treatment.

T cell immunity to measles viral proteins in infants and adults after measles immunization.

Vaccination of infants against measles remains of global importance, and proposed new vaccine strategies include the use of measles proteins or synthetic peptides as immunogens. We studied cell-mediated immunity to whole measles antigen and measles proteins in immune adults and infants after measles vaccine. Further, we measured CD8+ T cell responses to peptide pools corresponding to the nucelocapsid (N) measles protein in adults given measles vaccine. Cell-mediated immune responses to three of four measles proteins were equivalent to those against whole measles antigen in immune adults. Responses to the fusion (F) protein were lower in infants compared to whole measles antigen (p < or = 0.03). Infant responses to both whole measles antigen and the F protein were lower compared with these responses in adults (p < or = 0.001). CD8+ T cell responses to N peptide pools varied, and differed between immune HLA-A2-positive individuals compared with naive and HLA-A2-negative subjects after measles vaccination. The measles-specific T cell adaptive response of infants is limited compared to adults, including responses to the F protein.

Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme.

Despite the most aggressive medical and surgical treatments, glioblastoma multiforme remains incurable with a median survival of <1 year. We investigated the antitumor potential of a novel viral agent, an attenuated strain of measles virus (MV), derived from the Edmonston vaccine lineage, genetically engineered to produce carcinoembryonic antigen (CEA). CEA production as the virus replicates can serve as a marker of viral gene expression. Infection of a variety of glioblastoma cell lines including U87, U118, and U251 at MOIs 0.1, 1, and 10 resulted in significant cytopathic effect consisting of excessive syncycial formation and massive cell death at 72-96 h from infection. terminal deoxynucleotidyltransferase-mediated nick end labeling assays demonstrated the mechanism of cell death to be predominantly apoptotic. The efficacy of this approach in vivo was examined in BALB/c nude mice by using both s.c. and intracranial orthotopic U87 tumor models. In the s.c. U87 model, mice with established xenografts were treated with a total dose of 8 x 10(7) plaque forming units of MV-CEA, administered i.v. Mice treated with UV light inactivated MV, and untreated mice with established U87 tumors were used as controls. There was statistically significant regression of s.c. tumors (P < 0.001) and prolongation of survival (P = 0.007) in MV-CEA treated animals compared with the two control groups. In the intracranial orthotopic U87 model, there was significant regression of intracranial U87 tumors treated with intratumoral administration of MV-CEA at a total dose of 1.8 x 10(6) plaque forming units as assessed by magnetic resonance image (P = 0.002), and statistically significant prolongation of survival as compared with mice that received UV-inactivated virus and untreated mice (P = 0.02). Histological examination of brains of MV-CEA-treated animals revealed complete regression of the tumor with the presence of a residual glial scar and reactive changes, mainly presence of hemosiderin-laden macrophages. In addition, CEA levels in the peripheral blood in both the s.c. and orthotopic models increased before tumor regression, indicating viral gene expression, and returned to normal when the tumors regressed. Ifnar(ko) CD46 Ge transgenic mice, susceptible to MV infection, were used to assess central nervous system toxicity of MV-CEA. Intracranial administration of MV-CEA into the caudate nucleus of Ifnar(ko) CD46 Ge did not result in clinical neurotoxicity. Pathologic examination demonstrated limited microglial infiltration surrounding the injection site. In summary, MV-CEA has potent antitumor activity against gliomas in vitro, as well as in both s.c. and orthotopic U87 animal models. Monitoring CEA levels in the serum can serve as a low-risk method of detecting viral gene expression during treatment, and could allow dose optimization and individualization of treatment.

Neutralization of measles virus wild-type isolates after immunization with a synthetic peptide vaccine which is not recognized by neutralizing passive antibodies.

The sequence H379-410 of the measles virus haemagglutinin (MV-H) protein forms a surface-exposed loop and contains three cysteine residues (Cys-381, Cys-386 and Cys-394) which are conserved among all measles isolates. It comprises the minimal sequential B cell epitope (BCE) (H386-400) of the neutralizing and protective MAb BH6 that neutralizes all wild-type viruses tested. The aim of this study was to design synthetic peptides which induce neutralizing antibodies against MV wild-type isolates. Peptides containing one or two copies of T cell epitopes (TCE) and BCEs of different lengths (H386-400, B(CC); H379-400, B(CCC)), in different combinations and orientations were produced and iteratively optimized for inducing neutralizing antibodies. Peptides with the shorter BCE induced sera that cross-reacted with MV but did not neutralize. The longer BCE containing the three cysteines (B(CCC)) and two homologous TCE were required for neutralization activity. These sera neutralized wild-type strains of different clades and geographic origins. Neutralizing serum was also obtained after immunization with human promiscuous TCEs. Furthermore B(CCC)-based peptides were fully immunogenic even in the presence of pre-existing MV-specific antibodies. The results suggest that subunit vaccines based on such peptides could potentially be used to actively protect infants against wild-type viruses irrespective of persisting maternal antibodies.

Ex vivo analysis of cytotoxic T lymphocytes to measles antigens during infection and after vaccination in Gambian children.

The study of cytotoxic T cell responses to measles antigens during infection and after vaccination may provide insight into the immunopathology of the infection. It will also provide a knowledge of the immunity conferred by wild or attenuated virus, which will help in the design of new vaccines. Direct cytotoxic T cell responses, which did not require in vitro restimulation, were measured from peripheral blood by a standard 51Cr-release assay in 35 patients with acute measles, using HLA class I matched allogeneic B cells as targets. 77% showed specific responses to measles fusion protein, 69% to the hemagglutinin, and 50% to the nucleoprotein. These responses, which were related to severity of disease and history of previous vaccination, had waned by 14-24 wk after measles when memory responses to the same antigens could be elicited by restimulation in 71% of the 13 patients tested. A similar pattern followed vaccination: direct cytotoxic responses to fusion and hemagglutinin proteins were shown in 70% of the 20 children tested while 50% responded to the nucleoprotein. These responses, which were mediated by both CD8(+) and CD4(+) cells, faded over 6 wk when memory responses could be restimulated. Thus, a vigorous cytotoxic T lymphocyte response to fusion, hemagglutinin, and nucleoproteins is important in both natural and vaccine-induced immunity to measles.

Morbillivirus downregulation of CD46.

There is evidence that CD46 (membrane cofactor protein) is a cellular receptor for vaccine and laboratory-passaged strains of measles virus (MV). Following infection with these MV strains, CD46 is downregulated from the cell surface, and consequent complement-mediated lysis has been shown to occur upon infection of a human monocytic cell line. The MV hemagglutinin (H) protein alone is capable of inducing this downregulation. Some wild-type strains of MV fail to downregulate CD46, despite infection being prevented by anti-CD46 antibodies. In this study we show that CD46 is also downregulated to the same extent by wild-type, vaccine, and laboratory-passaged strains of rinderpest virus (RPV), although CD46 did not appear to be the receptor for RPV. Expression of the RPV H protein by a nonreplicating adenovirus vector was also found to cause this downregulation. A vaccine strain of peste des petits ruminants virus caused slight downregulation of CD46 in infected Vero cells, while wild-type and vaccine strains of canine distemper virus and a wild-type strain of dolphin morbillivirus failed to downregulate CD46. Downregulation of CD46 can, therefore, be a function independent of the use of this protein as a virus receptor.

Adverse impact of infections on antibody responses to measles vaccination.

Antibody titres were determined in 102 Thai infants who were vaccinated at 9-months of age during the respiratory disease season. The symptom densities of illnesses at or following vaccination, including rhinorrhea and diarrhea, were significantly lower among seroconverters, although the simple presence or absence of specific symptoms was not significantly related to seroconversions. Logistic regression indicated that neutralization test antibody titres below the median titre of 1:80 following vaccination were significantly more frequent among those with rhinorrhea when vaccinated and among those with diarrhea after vaccination. Compared with a referent group without these symptoms, titres were lower in those who had rhinorrhea when vaccinated, rhinorrhea during the first week post vaccination, and diarrhea in either of the two follow-up weeks. Illnesses concurrent or subsequent to measles vaccination adversely affected antibody responses in these study objects.

Induction of systemic immune responses to measles virus synthetic peptides administered intranasally.

A systemic antibody response was induced when a chimeric peptide containing two copies of a promiscuous T-cell epitope and one copy of a B-cell epitope (TTB) from the fusion protein of measles virus (MV) was administered to mice intranasally without adjuvant. A higher antibody titre was produced when the peptide was administered intranasally with cholera toxin B subunit (CTB) as an adjuvant and these antibodies crossreacted with the MV. Furthermore, splenocytes from intranasally immunized mice proliferated in vitro in the presence of the TTB peptide. The immune response following intranasal immunization with the peptide was influenced by the MHC haplotype of the strain of mice used. Thus CBA and BALB/c mice were high responders whereas C57BL/6 mice were low responders. Although peptide administered intranasally with CTB to CBA mice induced an immune response, no significant protection was observed against intra-cranial challenge with canine distemper virus which is antigenically related to MV.

Passively administered antibody suppresses the induction of measles virus antibodies by vaccinia-measles recombinant viruses.

We have used vaccinia-measles recombinant viruses to study vaccination in the presence of pre-existing antibody. When mice were vaccinated with recombinants expressing either the haemagglutinin (H) or fusion (F) measles virus (MV) proteins, the humoral response to the MV protein was suppressed by passively administered polyclonal antibody. However, individual monoclonal antibodies (H or F) did not affect the response. Mice whose anti-MV antibody response to H or F was initially suppressed by passive administration of anti-MV antibody were revaccinated 120 days later and gave a normal humoral response to the MV proteins. The VV-H recombinant induces a strong class I CTL response in Balb/c mice. This was not affected by the presence of levels of anti-MV antibody which inhibited the humoral response.

Measles antibodies in women and infants in the vaccine era.

The present investigation was done to determine whether measles enzyme immune assay (EIA) absorbency values were lower in women born in the vaccine era after 1963 and their infants in an upstate New York metropolitan area, an area of low measles incidence during the past 10 years compared with women born before the measles vaccine era who had natural measles. Aliquots of 202 sera from mother-infant pairs collected for other purposes from November 1990 to June 1991 at Albany Medical Center Hospital were tested by EIA. The demographic data available for analysis were maternal age and infant gestational age. Measles mean absorbency values were analyzed according to maternal age. Of 202 mother-infant pairs, 30% of mothers and 17% of their infants were seronegative (EIA < 0.16). Mothers born before 1963 and their infants had significantly higher mean EIA absorbency values than mothers born after 1963 and their infants (P < 0.002). The percent seropositive for measles antibodies by EIA for mothers born before 1963 and their infants, 87% and 94%, respectively, was significantly higher than the percent seropositive for mothers born after 1963 and their infants, 61% and 69%, respectively (P = 0.0001). Since the mean measles antibodies as measured by EIA absorbency were significantly lower in the mothers born after 1963 and their infants compared with women born before the vaccine era, the strategy for measles control in the future may have to include lowering the age of infant immunization.

Quality standard for assurance of measles immunity among health care workers. Infectious Diseases Society of America.

OBJECTIVE: The objective of this quality standard is to prevent nosocomial transmission of measles by assuring universal measles-mumps-rubella (MMR) vaccination of all health care workers who lack immunity to measles. Although the primary emphasis is on health care workers in hospitals, those at other sites, such as clinics, nursing homes, and schools, are also included. It will be the responsibility of designated individuals at these institutions to implement the standard. OPTIONS: We considered advocating the use of measles vaccine rather than MMR vaccine but chose the latter because it also protects against mumps and rubella and because it is more readily available. OUTCOMES: The desired outcome is a reduction in the nosocomial transmission of measles. EVIDENCE: Although direct comparative studies are lacking, nosocomial outbreaks of measles have been reported (as recently as 1992) in institutions where measles immunization of nonimmune health care workers is not universal, whereas such outbreaks have not been reported in institutions with universal immunization. VALUES AND VALIDATION: We consulted more than 50 infectious-disease experts from the fields of epidemiology, government, medicine, nursing, obstetrics and gynecology, pediatrics, and surgery. In light of disagreement regarding the implementation of the standard, we used group discussions to reach a consensus. BENEFITS, HARMS, AND COSTS: The consequences of the transmission of measles (and of mumps and rubella) in a health care institution include not only the morbidity and mortality attributable to the disease but also the significant cost of evaluating and containing an outbreak and the serious disruption of regular hospital routines when control measures are instituted. The potential harm to health care workers after the implementation of the standard consists of untoward effects of MMR vaccine, although the reactions of vaccinees should be minimal with adherence to recommended vaccination procedures. Implementation of the standard should entail no expense to health care workers; the precise cost to institutions is unknown, but the expense would be mitigated by the prevention of measles outbreaks. RECOMMENDATIONS: We recommend MMR vaccination of all health care workers who lack immunity to measles. SPONSORS: The Quality Standards Subcommittee of the Clinical Affairs Committee of the Infectious Diseases Society of America (IDSA) developed the standard. The subcommittee was composed of representatives of the IDSA (P.A.G. and J.E.M.), the Society for Hospital Epidemiology of America (R.P.W.), the Surgical Infection Society (E.P.D.), the Pediatric Infectious Diseases Society (P.J.K.), the Centers for Disease Control and Prevention (W.J.M.), the Obstetrics and Gynecology Infectious Diseases Society (R.L.S.), and the Association of Practitioners of Infection Control (T.L.B.). Funding was provided by the IDSA and the other cooperating organizations. The standard is endorsed by the IDSA.

Prior infection by respiratory syncytial virus or parainfluenza viruses augments virus-specific IgG responses induced by the measles/mumps/rubella vaccine.

We found previously that immunizing cyclophosphamide-treated mice with one Paramyxoviridae virus mixed with dimethyl dioctadecyl ammonium bromide induces T cells which apparently also recognize other Paramyxoviridae viruses. This finding and the fact that respiratory syncytial virus (RSV) and parainfluenza viruses (PIVs) infect children early in life led us to ask if prior RSV or PIV infections influence the antibody response to measles and mumps vaccine viruses. Detection of virus-specific IgG in serum specimens collected randomly or at defined times after measles/mumps/rubella (MMR) vaccination was done with solid-phase enzyme immunoassays. The antibody-binding data obtained were converted to serum antibody titers by an immunoassay curve-fitting computer program. Prior infection by RSV and PIVs correlated with an augmented IgG response not only to measles and mumps virus, but also to rubella virus. Furthermore, the augmentation was greater for responders below the median response. These data show that common early childhood viral infections can influence immunity induced by the MMR vaccine.

Vacunas anti-sarampión / Vaccines anti-measles

El sarampión es una enfermedad infecciosa causada por un virus con RNA de la familia de los paramixovirus. Aunque generalmente es benigna en la niñez, a veces se complica con infecciones secundarias y se le ha implicado como agente etiológico de la panencefalitis subaguda esclerosante, que es una expresión tardía de una infección sarampionosa latente. Debido a que este virus sólo infecta a seres humanos, su control o erradicación son situaciones que pueden hacerse posibles a través de la vacunación específica. Los subtítulos que componen este trabajo son: Cuadro clínico, Definición de caso, Complicaciones, El agente etiológico; Transmisión, epidemiología. El influjo de la vacunación; Sarampión y vacunación en México, El sarampión en los Estados Unidos, El problema continental, El sarampión en el ámbito universal, Vacunas antisarampionosas: A.Vacunas "vivas" atenuadas, B.Vacunas sobreatenuadas, C.Vacunas "muertas"; Especificaciones para las vacunas antisarampionosas de uso corriente, y Vacunas parenterales de alto título. Experiencias recientes

Interferência entre as vacinas anti-sarampo e antipoliomielite / Interference between measles and polio vaccines

O objetivo da presente pesquisa foi avaliar se a administraçäo prévia de vacina oral antipoliomielite, tipo Sabin (VOP-Sabin), interfere na eficácia sorológica da vacina do sarampo. Com essa finalidade estudaram-se 117 crianças, de nove meses de idade, que receberam vacina de vírus vivo atenuado do sarampo (cep BIKEN CAM 70) no período de quatro semanas, ou menos, após terem recebido vacina oral antipoliomielite (VOP-Sabin), e 88 crianças, da mesma faixa etária mas sem vacinaçäo recente com a VOP-Sabin, como controle. Os anticorpos IgG para o sarampo foram pesquisados mediante a reaçäo de imunofluorescência indireta. A proporçäo de soroconversäo para a vacina do sarampo foi de 19/23 (82,6%) nas crianças que tinham recebido a VOP-Sabin 2 a 6 dias antes; 29/37 (78,4%), nas que receberam VOP-Sabin 9 a 13 dias antes; 32/42 (76,2%), nas vacinadas com a VOP-Sabin 16 a 20 dias antes; e 12/15 (80,0%), nas vacinadas com intervalos de 23 a 26 dias. A proporçäo de soroconversäo no grupo controle (vacinadas quatro semanas ou mais após a VOP-Sabin) foi de 68/88 (77,8%) e a comparaçäo destas proporçöes näo mostrou diferenças estatisticamente significativas. Os resultados obtidos näo demonstraram, portanto, uma menor eficácia sorológica para a vacina do sarampo em crianças previamente vacinadas contra a pólio que recebram a vacina Sabin durante as quatro semanas anteriores