From: matthew@ooc.uva.nl (Matthew Lewis)
Subject: Conference newspaper - Wednesday 22 July - part 1
Note: non-commercial reproduction.
Archive-Number: 5757
Organization: Center for Innovation and Cooperative Technology, University of Amsterdam
Date: 22 Jul 92 16:39:39 GMT

Hello all,

Here is the Conference newspaper, Wednesday 22 July.  This paper 
cones to you courtesy of HIVNET, a Dutch organisation that has set 
up a network of BBS systems to spread information about HIV and 
AIDS.  The paper is available due to the kind cooperation of the 
Aids Congress Foundation.

**********************************************************
Salk reveals dramatic new vaccine theory 
by Sharon Kingman

Jonas Salk, whose pioneering work led to the development of a 
vaccine against poliomyelitis in 1954, has put forward a new theory 
that could hold the key to a vaccine against not only HIV, but also 
many other parasitic diseases including malaria. 
He developed the hypothesis after an experiment on monkeys 
showed that those given an inactivated HIV vaccine to induce the 
highest levels of antibodies and cell-mediated immunity failed to 
resist infection. Salk says he then realised it was pointless pursuing 
that path. 
His theory relies on the observation that the first reaction of the 
immune system after infection is among its T cells. This cell-
mediated immunity is called the TH1 response. An example is the 
reaction known as delayed type hypersensitivity, when a red wheal 
appears on the skin following injection of an antigen. 
As time after infection increases, the other "arm" of the immune 
system swings into action, with the production of antibodies. This 
humoral immunity is called the TH2 response. 
Studies by other groups of workers have suggested to Salk that the 
way to make a vaccine against HIV is to find a way to freeze the 
immune system in the TH1 response. 
Salk quotes a study by Bretscher and colleagues in support of this 
theory. These researchers injected one group of mice with a small 
dose of the organism that causes leishmaniasis and a second group 
with a large dose. The first group had a good delayed type 
hypersensitivity reaction while the second group had a stronger 
antibody response. When challenged with the infectious agent, 
however, only the animals in the first group resisted infection. 
Other researchers, led by Bloom, have shown that in patients with 
leprosy, relative resistance to the disease is associated with cell-
mediated immunity, while those who produce antibodies are highly 
susceptible.   
Work by Gene Shearer and his colleague at the National Institutes of 
Health in the US backs up the theory. Shearer found that 
individuals who remained HIV-negative when tested with the highly 
sensitive polymerase chain reaction for HIV - despite having been 
at high risk of HIV infection - had good cell-mediated responses 
against HIV while remaining antibody negative. 

Skin reaction
Salk has also looked at a cohort of HIV-positive patients who 
received his candidate vaccine based on inactivated HIV. About half 
of them had a local skin reaction when vaccinated, indicating a 
delayed type hypersensitivity reaction. This group has done much 
better clinically than the patients who did not respond in this way. 
Salk, who now works at the Salk Institute in La Jolla, California, 
says these data, taken together, suggest that the way to make a 
vaccine against HIV is to induce a cell-mediated response with an 
extremely small dose - probably measured in microgrammes. 
Vaccines that induce neutralising antibodies are directed against 
cell-free viruses. But HIV is different, similar to an intracellular 
parasite.
Salk agrees that if this approach works, it would be applicable to 
vaccines for other parasitic diseases.
The aim now is to find out how to lock the cell-mediated reaction 
so that the subsequent production of antibodies is prevented. Salk 
is conducting studies looking at which immunogens to use, which 
adjuvants, what doses and what timing. 
"We have to figure out a way of keeping the immune system in the 
TH1 mode. Even if that is difficult, we will find a way." 
*********************************************************
Activists slam NIH research plans
By Cindy Patton

An independent audit by the Treatment Action Group of New York 
has blamed administrative procedures at the National Institutes of 
Health in the US for duplicating or omitting research, hampering 
the progress in basic research and the development of new 
treatments. 

Treatment Action Group (TAG) is an activist organisation that 
monitors both public and private AIDS research and provides 
consumers with information about how research is administered.
Spencer Cox, speaking for the group, said there was underfunding 
and a lack of central coordination by NIH of 3,000 grants, contracts 
and internal projects, costing $800 million in fiscal 1991. This had 
resulted in duplication of studies and failure to pursue promising 
leads. 
The report says that virological research has been emphasized at 
the expense of immunology. Other areas that have been neglected 
include research into gynaecology, oncology and what Cox calls the 
"orphan diseases" - HIV wasting syndrome and neurological 
complications.
Cox said: "We know a lot about HIV and almost nothing about AIDS. 
We still don't know how you go from being seropositive to 
expressing the symptoms related to AIDS."
The 60-page report concludes that general decreases in basic 
scientific research over the past decade, combined with the failure 
of the AIDS research budget to keep up with inflation, mean that 
fewer dollars have to do more work, despite the continuing rapid 
rise in the number of AIDS cases. 
NIH's five-year plan lacks priorities, deadlines and clear criteria for 
evaluating projects, the document says.
TAG believes that the reason for the problem is that each 
specialised area of research, organised within institutes at the NIH, 
is virtually autonomous, "like a fiefdom". This makes it difficult to 
direct overall research priorities and monitor duplication of 
projects.
The NIH should bring all AIDS-related projects now conducted by 
its various branches directly under the Office of AIDS Research 
(OAR), which currently oversees only about half of them, the report 
says. The office has no direct mechanism for coordinating the 
autonomous institutes in order to reduce duplication and work 
toward a common research plan.
The report recommends increasing or even doubling the total NIH 
budget, with the bulk of funds going to research on AIDS, cancer 
and Alzheimer's disease.
There should also be a shift in research priorities, the report says, 
refocusing on pathogenesis and immunology and, in particular, 
directing attention to work on cytokine inhibitors and synthetic 
immune modulators.
The report, funded from the general operating funds of TAG and a 
$10,000 grant from Burroughs-Wellcome, reviewed projects and 
contracts of the NIH's AIDS programme in fiscal year 1991, 
government reports reviewing the progress of AIDS treatment 
research and making recom-mendations for the future, and the list 
of programmes which could not be funded for fiscal year 1993 due 
to presidential budget cuts. The audit was slow because accounts of 
projects from different government sources varied considerably, 
requiring researchers to cross-check their lists of grants.
World AIDS News was unable to contact senior NIH officials for 
comment last night.
*********************************************************
Mystery syndrome: the only mystery was why everyone got excited  
by William Check

What was rumoured to be  the beginning of a new phase to the AIDS 
epidemic turned out to be a rare and vaguely defined immune 
deficiency syndrome with no evidence for transmission. At a 
Recent Reports session specially convened yesterday, Dr Jeffrey 
Laurence, of Cornell Medical College, described five patients with 
progressive immune deficiency and no evidence of infection with 
HIV or any other agent. A report on the cases just appeared in 
Newsweek, prompting Dr James Curran, director of HIV/AIDS at 
the US National Centers for Disease Control, to ask "What does 
Newsweek know that we don't know?" 
Following Laurence's presentation, Curran described six similar 
cases reported to the CDC over the past few years. Other scientists 
added sporadic instances of HIV-negative patients with moderate-
to-severe immune deficiency and no evidence for HIV infection. 
Curran concluded, "I think [this syndrome] is real, but I don't know 
if it's new." He also said that it must be uncommon. Laurence 
agreed that it is "exceedingly rare". The two also agreed that these 
are not AIDS cases.
Laurence defined his cases as "a progressive, sustained immuno-
suppression." 
Two patients' CD4 counts had dropped to 270 and 280 and 
continued to fall. Three had very low CD4 counts and opportunistic 
infections - cytomegalovirus colitis, Kaposi's sarcoma, pneumocystis 
carinii pneumonia, and herpes zoster. A few had known risk factors 
for HIV transmission.  

Most cases reported to CDC have been similar to Laurence's. CDC 
did not report these cases because too many questions remained 
and "We wanted to answer them through the usual scientific 
channels," Curran said.  
Addressing fears that the syndrome is due to a variant of HIV not 
detected by current tests, Dr James Allen, of CDC, said, "I think you 
can rest assured that the blood supply is safe in countries that have 
a screening system in place."
"Should we have reported a year ago when we first had three 
cases?" Curran asked the AIDS researchers. "Yes", came the 
resounding cries. He agreed to write up CDC's information and to 
issue a call for additional cases. 
*********************************************************
Tight Isolation, Fast Treatment Urged for MDR-TB 
By Janis Kelly

Multi-drug-resistant tuberculosis (MDR-TB) poses a "significant risk 
to health care workers" said            Dr Michael Mullen of Cabrini 
Medical Center in New York, in yesterday's session on Tuber-
culosis.  
Mullen urged clinicians to strictly isolate all HIV-positive patients 
who present with fever and respiratory symptoms that suggest TB.  
"Isolation must continue until there is a clear response to 
treatment and follow-up monitoring of respiratory isolates must be 
done. Extreme caution must be practiced when patients are on 
treatments such as aerosolized pentamidine."  
At Cabrini Medical Center, MDR-TB jumped from 8 of 132 TB cases 
during 1982-87 to 24 of 74 cases between December 1990 and       
May 1991. Mortality was 79%, despite intensive treatment, Mullen 
said. Dr Margaret Fischl of the University of Miami, Florida, USA, 
reported a sudden upsurge of MDR-TB at that institution in 1990. 
Forty-seven of the 62 cases (76%) were in AIDS patients.  
Both researchers said that markers of MDR-TB were continued 
fever, worsening lung infiltrates, and continued or intermittent 
positive cultures, despite treatment with 4 or more drugs. 
Patients with non-resistant TB should respond within 5-7 days of 
treatment.  Patients with MDR-TB were also more likely to have 
extrapulmonary tuberculosis, as well as atypical chest X-rays. Three 
of Mullen's patients actually had normal chest X-rays.   
Nosocomial spread was implicated in both reports. At Cabrini, 14 of 
15 isolates were genetically identical.  At Miami, patients most 
likely to have MDR-TB had AIDS and had been treated in the 
outpatient clinic or had received aerosolized pentamidine.  
"We concluded from this that we were dealing with nosocomial 
transmission of MDR-TB," Fischl said, "probably in the crowded 
waiting rooms of our outpatient clinic." Like Mullen, she urged 
treating all HIV patients with TB as though they have MDR-TB until 
it can be determined whether they have resistant strains. In New 
York City this can take up to 9 weeks.  
*********************************************************
New monkey models may speed research
By Janis Kelly
There is renewed hope that  a good animal model for HIV may soon 
help scientists develop vaccines and new drugs.  Researchers 
announced yesterday that HIV-1 can infect a species of macaque 
monkey and that an artificial hybrid of HIV and SIV can infect a 
second species of monkey.

Until now, the only animals that researchers have been able to 
infect with HIV is the chimpanzee, a protected species in short 
supply. But chimpanzees have not developed AIDS.
The need for a model based on cheaper and smaller animals 
became more and more urgent as scientists developed more 
candidate vaccines and antiviral agents that they wanted to evaluate. 
Two new approaches to the animal model problem presented 
yesterday may help to solve this problem. The first discovery is that 
HIV-1 will infect Macaca nemestrina, will kill this monkey's 
lymphocytes, and will produce both cell-associated and free virus 
(see electron micrograph below). 
Dr Michael Agy of the Regional Primate Research Center in Seattle 
infected peripheral blood mononuclear cells (PBMCs) from 
macaques with HIV. He found that the virus replicated in cells from   
M. nemestrina but not in those from M. fascicularis or M. mulatta. 
HIV strains including LAI, NL4-3, and JR-CSF all replicated in the 
cells of M. nemestrina. 
Two individuals of this species, inoculated with HIV-1 LAI, 
produced strong antibody responses to HIV proteins. Virus could 
be recovered from both animals at two to 24 weeks after 
inoculation. DNA derived from HIV-1 was present in the animals' 
PBMC at least 52 weeks after infection.  
No animals have become ill, apart from initial lymphadenopathy, but 
that may be a function of time.  There has been no net decrease in 
CD4 cells, despite the fact that the virus kills these cells in vitro.  
While this study shows that these monkeys are a new model system 
for HIV, several researchers at the session on animal models 
reported difficulty obtaining supplies of this species.   
The second approach to producing a model for vaccine and drug 
testing involves sticking together pieces of the human and monkey 
viruses.   Drs Norman Letvin of the New England Regional Primate 
Research Center in the US and Masanori Hayami of Kyoto 
University in Japan both presented work on these artificially 
constructed HIV/SIV chimeras. The engineered viruses could 
directly infect cynomolgus macaques as well as blood cells exposed 
in vitro. So far, there are few signs of disease in the animals in 
either study. 
In response to a question from Dr Luc Montagnier of the Institut 
Pasteur in Paris, Letvin said that his virus is cytopathic for CD4 cells 
and induces syncytia formation.  
Since HIV/SIV chimeric viruses can infect monkeys, the question 
of additional safety precautions for  researchers working with them 
was raised by Dr Albert Osterhaus of the National Institute of Public 
Health in the Netherlands. The possibility that the artificial viruses 
might infect humans as easily as monkeys has not yet been ruled 
out.
*********************************************************

-- 
Matthew Lewis, University of Amsterdam		Grote Bickersstraat 72
+31-20-52 51 220				1013 KS  Amsterdam
Internet: matthew@ooc.uva.nl			The Netherlands
Newsgroups: sci.med.aids