scholarly journals A recombinant measles virus vaccine strongly reduces SHIV viremia and virus reservoir establishment in macaques

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Patrycja Nzounza ◽  
Grégoire Martin ◽  
Nathalie Dereuddre-Bosquet ◽  
Valérie Najburg ◽  
Leslie Gosse ◽  
...  
Keyword(s):  
Measles Virus ◽  
Viral Vector ◽  
Measles Vaccine ◽  
Cell Infection ◽  
Log Reduction ◽  
Immunodeficiency Virus ◽  
Vaccine Antigens ◽  
Env Antigens ◽  
Cellular Immune ◽  
Human Vaccine

AbstractReplicative vectors derived from live-attenuated measles virus (MV) carrying additional non-measles vaccine antigens have long demonstrated safety and immunogenicity in humans despite pre-existing immunity to measles. Here, we report the vaccination of cynomolgus macaques with MV replicative vectors expressing simian-human immunodeficiency virus Gag, Env, and Nef antigens (MV-SHIV Wt) either wild type or mutated in the immunosuppressive (IS) domains of Nef and Env antigens (MV-SHIV Mt). We found that the inactivation of Nef and Env IS domains by targeted mutations led to the induction of significantly enhanced post-prime cellular immune responses. After repeated challenges with low doses of SHIV-SF162p3, vaccinees were protected against high viremia, resulting in a 2-Log reduction in peak viremia, accelerated viral clearance, and a decrease -even complete protection for nearly half of the monkeys- in reservoir cell infection. This study demonstrates the potential of a replicative viral vector derived from the safe and widely used measles vaccine in the development of a future human vaccine against HIV-1.

scholarly journals Frequency of Measles Virus-Specific CD4+ and CD8+ T Cells in Subjects Seronegative or Highly Seropositive for Measles Vaccine

2003 ◽  
Vol 10 (3) ◽  
pp. 411-416 ◽  
Author(s):  
Inna G. Ovsyannikova ◽  
Neelam Dhiman ◽  
Robert M. Jacobson ◽  
Robert A. Vierkant ◽  
Gregory A. Poland
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Measles Virus ◽  
Vaccine Virus ◽  
Th2 Cells ◽  
Cell Mediated Immunity ◽  
Median Frequency ◽  
Measles Vaccine ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT The protective effect of measles immunization is due to humoral and cell-mediated immune responses. Little is known about cell-mediated immunity (CMI) to measles vaccine virus, the relative contribution of CD4+ and CD8+ T cells to variability in such immune responses, and the immunologic longevity of the CMI after measles vaccination in humans. Our study characterizes cellular immune response in subjects seronegative or highly seropositive for measles vaccine immunoglobulin G-specific antibody, aged 15 to 25 years, previously immunized with two doses of measles-mumps-rubella II vaccine. We evaluated the ability of subjects to respond to measles vaccine virus by measuring measles virus-specific T-cell proliferation. We examined the frequencies of measles virus-specific memory Th1 and Th2 cells by an ELISPOT assay. Our results demonstrated that proliferation of T cells in seronegative subjects was significantly lower than that for highly seropositive subjects (P = 0.003). Gamma interferon (IFN-γ) secretion predominated over interleukin 4 (IL-4) secretion in response to measles virus in both groups. The median frequency of measles virus-reactive CD8+ T cells secreting IFN-γ was 0.09% in seronegative subjects and 0.43% in highly seropositive subjects (P = 0.04). The median frequency of CD4+ T cells secreting IL-4 in response to measles virus was 0.03% in seronegative subjects and 0.09% in highly seropositive subjects (P = 0.005). These data confirm the presence of measles virus-specific cellular immune responses post-measles vaccine immunization in humans. The detection of measles virus-induced IFN-γ and IL-4 production by ELISPOT can be used to identify measles virus-specific low-frequency memory T cells in subjects immunized with measles vaccine. These differences agree in directionality with the observed antibody response phenotype.

scholarly journals Protection against Simian Immunodeficiency Virus Vaginal Challenge by Using Sabin Poliovirus Vectors

2001 ◽  
Vol 75 (16) ◽  
pp. 7435-7452 ◽  
Author(s):  
Shane Crotty ◽  
Christopher J. Miller ◽  
Barbara L. Lohman ◽  
Martha R. Neagu ◽  
Lara Compton ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Vaccination Strategy ◽  
Vaccine Vector ◽  
Mucosal Antibody ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Lymphocyte Responses ◽  
Pronounced Reduction ◽  
Human Vaccine

ABSTRACT Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector. New poliovirus vectors based on Sabin 1 and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag,pol, env, nef, andtat in overlapping fragments. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV) were inoculated into seven cynomolgus macaques. All monkeys produced substantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte responses were detected in three of seven monkeys after vaccination. All 7 vaccinated macaques, as well as 12 control macaques, were challenged vaginally with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge. All 12 control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated monkeys we found no virological evidence of infection following challenge, indicating that these two monkeys were completely protected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to <103 copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six control animals developed clinical AIDS by 48 weeks postchallenge. In contrast, all seven vaccinated monkeys remained healthy as judged by all clinical parameters. These results demonstrate the efficacy of SabRV as a potential human vaccine vector, and they show that the use of a vaccine vector cocktail expressing an array of defined antigenic sequences can be an effective vaccination strategy in an outbred population.

Viral Vector Vaccines

2021 ◽  
Author(s):  
Valerie Oriol Mathieu ◽  
Mark van Ooij ◽  
Kerstin Lühn ◽  
Jeff Stoddard
Keyword(s):  
Immune Responses ◽  
Viral Vectors ◽  
Viral Vector ◽  
Genetic Material ◽  
Adenovirus Vector ◽  
Cellular Immune Responses ◽  
Host Cell Cytoplasm ◽  
Vaccine Antigens ◽  
Transfer Vectors ◽  
Cellular Immune

Viral vector vaccines use harmless, non-replicating or replicating viruses to deliver genetic material for production of vaccine antigens into host cell cytoplasm. While viral vector vaccines may theoretically induce life-long immunity with low antigen concentrations, their attenuation, safety and spread to the community are of concern. Vaccines based on recombinant viral vectors can induce both humoral and cellular immune responses. Adenovirus vectors are versatile gene transfer vectors that can be easily manufactured, and which may allow simultaneous expression of multiple antigens by a single vector construct. Adenovirus vector vaccines based on the adenovirus Ad26 vector have been widely used as vaccines against Ebola and COVID19 (see Chapters 44 and 56). A common concern of using viral vector vaccines is pre-existing immunity or induction of immunity against the vector itself, but in some circumstances it has no meaningful impact and it can be resolved in several ways. Several harmless viruses are already used as vectors for innovative vaccines and many more are in research.

scholarly journals Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge

2009 ◽  
Vol 83 (13) ◽  
pp. 6508-6521 ◽  
Author(s):  
Nancy A. Wilson ◽  
Brandon F. Keele ◽  
Jason S. Reed ◽  
Shari M. Piaskowski ◽  
Caitlin E. MacNair ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Chronic Phase ◽  
Structural Features ◽  
Viral Loads ◽  
Log Reduction ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune

ABSTRACT All human immunodeficiency virus (HIV) vaccine efficacy trials to date have ended in failure. Structural features of the Env glycoprotein and its enormous variability have frustrated efforts to induce broadly reactive neutralizing antibodies. To explore the extent to which vaccine-induced cellular immune responses, in the absence of neutralizing antibodies, can control replication of a heterologous, mucosal viral challenge, we vaccinated eight macaques with a DNA/Ad5 regimen expressing all of the proteins of SIVmac239 except Env. Vaccinees mounted high-frequency T-cell responses against 11 to 34 epitopes. We challenged the vaccinees and eight naïve animals with the heterologous biological isolate SIVsmE660, using a regimen intended to mimic typical HIV exposures resulting in infection. Viral loads in the vaccinees were significantly less at both the peak (1.9-log reduction; P < 0.03) and at the set point (2.6-log reduction; P < 0.006) than those in control naïve animals. Five of eight vaccinated macaques controlled acute peak viral replication to less than 80,000 viral RNA (vRNA) copy eq/ml and to less than 100 vRNA copy eq/ml in the chronic phase. Our results demonstrate that broad vaccine-induced cellular immune responses can effectively control replication of a pathogenic, heterologous AIDS virus, suggesting that T-cell-based vaccines may have greater potential than previously appreciated.

scholarly journals Comprehensive Epitope Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses Directed against the Entire Expressed HIV-1 Genome Demonstrate Broadly Directed Responses, but No Correlation to Viral Load

2003 ◽  
Vol 77 (3) ◽  
pp. 2081-2092 ◽  
Author(s):  
M. M. Addo ◽  
X. G. Yu ◽  
A. Rathod ◽  
D. Cohen ◽  
R. L. Eldridge ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Protein Subunits ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Total Magnitude ◽  
Cellular Immune ◽  
Hiv 1

ABSTRACT Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/106 PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

Measles Immunity After Revaccination: Results in Children Vaccinated Before 10 Months of Age

PEDIATRICS ◽  
1982 ◽  
Vol 69 (3) ◽  
pp. 332-335
Author(s):  
Calvin C. Linnemann ◽  
Mark S. Dine ◽  
Gary A. Roselle ◽  
P. Anne Askey
Keyword(s):  
Measles Virus ◽  
Geometric Mean ◽  
Lymphocyte Transformation ◽  
First Year ◽  
Cell Mediated Immunity ◽  
Measles Vaccine ◽  
Pediatric Practice ◽  
Antibody Titers ◽  
Measles Vaccination ◽  
First Year Of Life

Measles immunity was studied in children in a private pediatric practice who had been revaccinated because they had received their primary measles vaccination before 1 year of age. Antibody was measured in 72 of these children who had received the first injection of live measles virus vaccine at &lt;10 months of age, and the second at &gt;1 year of age. Of the 72 children, 29 (40%) had no detectable antibody and the geometric mean titer for the group was approximately 1:4. Of the children with low antibody titers, 15 were given a third injection of measles vaccine and five (33%) still did not respond. Cell- mediated immunity as indicated by lymphocyte transformation to measles antigen was measured in 11 of the children. Five (45%) had responses to measles antigen, but the responses did not correlate with the presence or absence of antibody. This study confirms the observation that revaccination is unsuccessful in many children who received measles vaccine in the first year of life, and shows that even a third injection of vaccine may fail to produce a significant antibody response.

MEASLES IMMUNIZATION INCORPORATED IN THE ROUTINE SCHEDULE FOR INFANTS: EFFICACY OF A COMBINED INACTIVATED-LIVE VACCINATION REGIMEN

PEDIATRICS ◽  
1964 ◽  
Vol 34 (6) ◽  
pp. 795-797
Author(s):  
Saul Krugman ◽  
Shirley Stone ◽  
Rose Hu ◽  
Harriet Friedman
Keyword(s):  
Virus Vaccine ◽  
Measles Virus ◽  
Gamma Globulin ◽  
Virus Disease ◽  
Indirect Evidence ◽  
Antibody Test ◽  
Vaccine Virus ◽  
Inactivated Vaccine ◽  
Measles Vaccine ◽  
Subclinical Disease

1. Live attenuated measles virus vaccine without gamma globulin was extremely well tolerated by infants 12 to 14 months of age if they received 3 doses of inactivated vaccine at about 2, 3, and 4 months of age. This phenomenon was observed in spite of no detectable antibody after inactivated vaccine and a consistent antibody response after live vaccine. 2. Three inoculations of inactivated vaccine appeared to have an attenuating effect on measles infection acquired within 9 months by 17 infants; at least 70% of these infants were proved to have a subclinical disease by serologic studies. 3. The failure to detect antibody following three inoculations of killed vaccine probably reflects the lack of sensitivity of the HI antibody test which was employed in this study. The attenuating effect of the killed vaccine on the natural disease and on the measles vaccine-virus disease provides indirect evidence of antibody formation. 4. If killed measles vaccine can be successfully incorporated with diphtheriapertussis-tetanus toxoid it should be a useful preparation for primary immunization during the first 6 months of life. However, it would be most important to complete the immunization with an inoculation of live attenuated measles-virus vaccine at 12 to 14 months of age.

scholarly journals Rash after measles vaccination: laboratory analysis of cases reported in São Paulo, Brazil

2002 ◽  
Vol 36 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Maria I Oliveira ◽  
Suely P Curti ◽  
Cristina A Figueiredo ◽  
Ana MS Afonso ◽  
Márcia Theobaldo ◽  
...  
Keyword(s):  
Measles Virus ◽  
Viral Infections ◽  
Parvovirus B19 ◽  
Study Data ◽  
Laboratory Analysis ◽  
Measles Vaccine ◽  
Etiological Diagnosis ◽  
Measles Vaccination ◽  
Clinical Differential Diagnosis ◽  
Rubella Vaccination

OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19) using ELISA commercial techniques, and human herpes virus 6 (HHV 6) using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR). RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months), had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17) HPV B19 infection; 76.5% (13 in 17) HHV 6 infection; 5.9% (1 in 17) rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.

scholarly journals Immunogenicity of Heterologous Prime-Boost Regimens Involving Recombinant Adenovirus Serotype 11 (Ad11) and Ad35 Vaccine Vectors in the Presence of Anti-Ad5 Immunity

2005 ◽  
Vol 79 (15) ◽  
pp. 9694-9701 ◽  
Author(s):  
Angelique A. C. Lemckert ◽  
Shawn M. Sumida ◽  
Lennart Holterman ◽  
Ronald Vogels ◽  
Diana M. Truitt ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recombinant Adenovirus ◽  
Human Populations ◽  
Vaccine Vectors ◽  
Adenovirus Serotype ◽  
Immunodeficiency Virus ◽  
High Prevalence ◽  
Boost Vaccine ◽  
Serotype 5 ◽  
Cellular Immune

ABSTRACT The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.

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