The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with ...matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.
480 participants were evenly randomized to receive either: DNA (4 mg i.m. by Biojector) at 0, 1 and 2 months, followed by rAd5 (10(10) PU i.m. by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost.
The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients.
The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.
ClinicalTrials.gov NCT00125970.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Road to an Effective HIV Vaccine Baden, Lindsey R; Dolin, Raphael
The New England journal of medicine,
04/2012, Letnik:
366, Številka:
14
Journal Article
Recenzirano
During the 30 years since the discovery of HIV as the cause of AIDS, efforts to develop a vaccine have faced immense challenges. First, naturally acquired immunity to protect against infection that ...results in disease, found with virtually all other known infectious agents, may not exist for HIV. Second, the best available experimental animal model for AIDS, the nonhuman primate, provides potentially important information but also has substantial limitations. Therefore, advancement in the field has put an extraordinarily high premium on data from human studies. Yet only three candidate HIV vaccines have completed clinical efficacy trials. The first of these . . .
Background. Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In ...particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans. Methods. In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed. Results. Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4⁺ T lymphocytes following vaccination by either histopathology or flow cytometry. Conclusions. These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation.
Remdesivir — An Important First Step Dolin, Raphael; Hirsch, Martin S
New England journal of medicine/The New England journal of medicine,
11/2020, Letnik:
383, Številka:
19
Journal Article
Recenzirano
Odprti dostop
In May 2020, Beigel et al. provided in the
Journal
the first report of an effective treatment for Covid-19, resulting from a rigorously designed and conducted clinical trial.
1
It is remarkable that ...a randomized, placebo-controlled trial of a potential antiviral treatment for a disease whose pathogenesis is still not fully defined was carried out at multiple international sites during a pandemic. Conducting such a clinical trial only a few months after SARS-CoV-2 was discovered was an extraordinary achievement. The reported clinical effect of intravenous remdesivir was relatively modest. In this issue of the
Journal
, the authors report the final results from that trial . . .
HIV-AIDS has emerged as an enormous, worldwide public health problem over the past 25 years. An estimated 33 million persons are infected with human immunodeficiency virus type 1 (HIV-1), and more ...than 7000 new infections occur every day.
1
Although major advances have been made in the treatment of HIV-1 infection and in certain behavioral approaches to the prevention of HIV infection, ultimately, control will most likely depend on the development and application of a safe and effective HIV vaccine.
Substantial effort is being expended to develop an HIV vaccine through a variety of approaches.
2
However, disappointing results have emerged from . . .
Norovirus infections are worldwide in distribution and affect all age groups. Dr. Raphael Dolin writes that the biologic, physicochemical, and epidemiologic features of noroviruses present a serious ...challenge for infection control.
Acute infectious gastroenteritis is an extremely common illness, second in frequency only to acute respiratory illness among North American families. Although it had long been suspected that such illnesses were caused by viruses, it was only after clinical and laboratory studies were carried out over the past three decades that causative viruses were identified.
1
,
2
Among the most prominent are a novel group of viruses originally referred to as Norwalk-like agents — named after Norwalk, Ohio, where an outbreak of illness was caused by the prototype agent — and now called noroviruses.
Noroviruses are small (26 to 35 nm), single-stranded . . .
The development of new drugs against human immunodeficiency virus type 1 (HIV-1) has resulted in combination therapy that can inhibit various steps of viral replication. Maraviroc is an example of a ...new class of such drugs that have a novel mechanism of action against HIV-1.
1
Maraviroc binds to the human chemokine receptor 5 (CCR5), which also serves as a coreceptor for a major phenotype of HIV-1, R5 tropic virus, and thereby interferes with an essential early step in viral replication. Maraviroc has shown activity both in vitro and in vivo against R5 HIV-1 strains. In two large-scale trials reported in . . .
A human immunodeficiency virus (HIV) vaccine remains a central component in the quest to control the worldwide epidemic. To examine the status of the development of HIV vaccines, we review the ...results of the efficacy trials carried out to date and the immunologic principles that guided them. Four vaccine concepts have been evaluated in HIV-1 vaccine efficacy trials, and the results of these trials have provided significant information for future vaccine development. While one of these trials demonstrated that a safe and effective HIV vaccine is possible, many questions remain regarding the basis for the observed protection and the most efficient way to stimulate it. Novel HIV vaccine strategies including induction of highly potent broadly neutralizing antibodies, use of novel homologous and heterologous vector systems, and vectored immunoprophylaxis seek to expand and build upon the knowledge gained from these trials.
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