A single dose of an antibody-based treatment can prevent human immunodeficiency virus (HIV) transmission from mother to baby, according to new nonhuman primate research. The findings (“Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity”) were recently published in Nature Communications. When that single dose is given is key, however. The study found rhesus macaque newborns did not develop the monkey form of HIV, called SHIV, when they received a combination of two antibodies 30 hours after being exposed to the virus.

Delaying treatment until 48 hours, on the other hand, resulted in half of the baby macaques developing SHIV when they were given four smaller doses of the same antibody cocktail. In comparison, the study found macaques that received the current standard HIV treatment—antiretroviral drugs—remained SHIV-free when they started a three-week regimen of that therapy 48 hours after exposure.

Vertical transmission accounts for most HIV infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. “We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48 h leads to tight control without adaptive immune responses in half of the animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30–48 h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed,” the investigators wrote.

“These promising findings could mean babies born to HIV-positive mothers can still beat HIV with less treatment,” said the study’s corresponding’s author, Nancy Haigwood, PhD, a professor of pathobiology and immunology in the Oregon Health & Science University (OHSU) School of Medicine, as well as the director at the Oregon National Primate Research Center at OHSU.

This is the first time a single dose of broadly neutralizing antibodies given after viral exposure has been found to prevent SHIV infection in nonhuman primate newborns, noted the scientists. Previous research by Haigwood, Ann Hessell, PhD, a research associate professor at OHSU, and others showed four doses of antibodies started 24 hours after exposure prevented SHIV infection, with all 10 of the baby primates in that study not having any SHIV virus for six months. Both studies used a combination of two antibodies called PGT121 and VRC07-523.

The new study also suggests a much shorter course of antiretroviral therapy given after virus exposure could prevent HIV transmission to newborns. Human babies born from HIV-positive mothers typically take the drug cocktail—a personalized regimen of multiple drugs taken daily—for about six weeks before being re-tested. If the tests are then positive, they likely need to take HIV drugs for the rest of their lives. But this study showed nonhuman primate newborns didn’t have SHIV after undergoing antiretroviral therapy for just three weeks starting 48 hours after exposure.

HIV-positive women typically take antiretroviral therapy drugs during pregnancy for their own health, as well as to prevent passing the virus onto their developing child. But mother-to-baby transmission sometimes still happens. Children born to HIV-positive mothers also are given antiretroviral therapy to further prevent infection. However, this drug cocktail can have many negative side effects, involves making special liquid formulations for newborns, and researchers worry about antiretroviral therapy’s long-term consequences for development.

Antibodies, however, generally aren’t toxic and can be modified to last a long time in the body, which reduces treatment frequency. This has led researchers to explore their potential to replace or supplement antiretroviral therapy for newborns with HIV-positive mothers as well as for HIV-positive adults.

Next, Haigwood and colleagues plan to see if different antibodies, or a combination of antibodies and antiretroviral therapy, could be even more effective. They also want to determine if the antibodies they evaluate actually eliminate HIV, or only prevent it from replicating. The research team has regularly shared their primate research findings with the scientific community, including those involved in the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, which is currently leading two trials evaluating a single antibody to treat HIV-exposed newborns.

The post Antibody Combination Prevents HIV Transmission from Mother to Infant appeared first on MyMedicPlus.

There are millions living with HIV and researchers have been working towards making a successful vaccine against the deadly infection for the past 35 years with no success. Now a new blueprint is being developed to prevent the infection.

A team of researchers from Duke University and Harvard have worked towards making a vaccine that can imitate a rare process in the immune system that is seen in persons with HIV. This process can help reduce the viral load of the body, explain the researchers.

The study results were published in the latest issue of the journal Science.

Researchers warn that this may be the first step in the development of an effective vaccine against the infection and there may be many bridges to cross before the final vaccine is ready for human use and is tried in large scale clinical trials.

Barton Haynes, director of the Duke Human Vaccine Institute, who was the lead author of the study said in a statement, “For the first 20 years after the virus was discovered, the field tried to make a vaccine using the techniques that all the successful measles, mumps, rubella, polio vaccines had been made within the past. And none of those worked.” He explained that the virus is constantly changing and thus every vaccine developed failed to generate antibodies that could fight the infection off.

The researchers explained in their work that in around 20 percent of the persons infected with HIV, the immune system makes a special protein called “broadly neutralizing antibodies” (bnAbs). These antibodies are powerful enough to remove the viruses in regions that remain same despite mutations. This means that the HIV may mutate but the antibodies would still be able to attack and remove them and not allow the viruses to replicate. These antibodies cannot cure a person with HIV however because some reservoirs of viruses remain within certain cells where the antibodies fail to reach them.

There have been studies where animal models of HIV have been injected with these antibodies and results showed that new infections could be prevented by these injections. This protection however did not last and was too short lived explain the researchers. To make an effective vaccine the researchers needed a shot that would provide long term protection from HIV infection.

Thus for this new study the team used technology of computer modelling and followed it up with lab testing to see if the mice and monkeys could train their immune systems to create these antibodies and fight off the infection. Haynes said, “We show a new way to design the HIV vaccine to guide the broadly neutralizing antibodies to go down paths they rarely go down on their own.”

They wrote that they “hypothesized that vaccination with immunogens that bind with moderate to high affinity to bnAb B cell precursors, and with higher affinity to precursors that have acquired improbable mutations, could initiate bnAb B cell lineages and select for key improbable mutations required for bnAb development.” They wrote in their results section, “…our immunogens elicited antibody responses in macaques and knock-in mice that exhibited the mutational patterns, structural characteristics, or neutralization profiles of nascent broadly neutralizing antibodies.”

They first designed HIV-1 envelope immunogens (moieties that could mimic the cover of an HIV-1 virus and stimulate the immune response). These immunogens were bound to bound precursor B cells at the CD4 binding site or else at the V3-glycan bnAb lineage. They then vaccinated lab macaques with the CD4 bound antibodies, They also used genetically modified mice called “knock in mice”. These mice had genes to secrete the needed bnAb. From these mice the isolated bnAbs were found to neutralize the HIV-1 global isolates. These bnAbs were found to kill the HIV-1 isolates despite their mutations, the team noted.

Other experts have lauded this approach saying that the body would be the best manufacturer of the antibodies that could fight off the HIV infection. This work is one third completed with development of essential antibodies that could fight off the infection. They hope to soon have the tools for an effective HIV vaccine.

The team wrote in conclusion, “…this study demonstrates a rational strategy for sequential immunogen design to circumvent the difficult roadblocks in HIV-1 bnAb induction by vaccination…This strategy of selection of specific antibody nucleotides by immunogen design can be applied to B cell lineages targeting other pathogens where guided affinity maturation is needed for a protective antibody response.”

Dr. John Mascola, director of the Vaccine Research Center at the National Institutes of Health (NIH) in a statement said that this new vaccine could be 80 to 90 percent effective and estimates that it would be ready for trials in large clinical trials in another five years.

The post Novel HIV vaccine shows promise appeared first on MyMedicPlus.