Neutralizing Antibodies Offer Clues for HIV Vaccine Research

Researchers have identified broadly neutralizing antibodies targeting variable regions of the HIV-1 envelope that controlled superinfection in a South African woman, according to a report in the March 2, 2014, online edition of Nature. Learning more about such antibodies and how they work may aid the development of preventive or therapeutic HIV vaccines.


Although the body produces antibodies in response to HIV infection, in most people the immune system is not able to control the virus. Some individuals, however, do manage to keep HIV in check, offering insight into what must be done to give other people this ability.

At an HIV community cure workshop preceding the Conference on Retroviruses and Opportunistic Infections (CROI 2014) this week in Boston, Romas Gelezunias from Gilead Sciences described several avenues of HIV cure research, including potent and broadly neutralizing monoclonal antibodies derived from HIV patients he dubbed "elite neutralizers."

Below is an edited excerpt from a press release issued by Wits University describing the Nature study in more detail.

New Research on Potent HIV Antibodies

March 3, 2014 -- The discovery of how a KwaZulu-Natal woman’s body responded to her HIV infection by making potent antibodies (called broadly neutralizing antibodies, because they are able to kill multiple strains of HIV from across the world), was reported today by the CAPRISA consortium of AIDS researchers jointly with scientists from the United States.

The study, published in the scientific journal Nature, describes how the research team found and identified these antibodies in her blood and then duplicated them by cloning the antibodies in the laboratory. The cloned antibodies were then used in a series of experiments in the laboratory to elucidate the pathway followed by her immune system to make these potent antibodies.

The South African researchers in the CAPRISA consortium, which includes scientists from Wits University, the National Institute for Communicable Diseases (NICD) in Johannesburg, the University of KwaZulu-Natal and the University of Cape Town, worked jointly with U.S. partners based at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and Columbia University in New York, to conduct this research.

"In this new publication, we have been able to isolate a broadly neutralizing antibody from this CAPRISA volunteer and trace its origins to understand exactly how it arose. This could lead to new HIV vaccine strategies that are able to stimulate the rare precursors of these protective antibodies," says Professor Lynn Morris, from the National Health Laboratory Service in the Wits School of Pathology who leads the research team at the NICD.

Professor Salim S. Abdool Karim, leader of the CAPRISA consortium and President of the Medical Research Council, commented, "The new insights gained from this KwaZulu-Natal woman into immune responses against HIV bring hope for future HIV prevention and treatment strategies. This woman, referred to as CAPRISA 256 (abbreviated to CAP256), is doing well on antiretroviral therapy and continues to attend the CAPRISA clinic regularly."

Just over a year ago, the same team of South African researchers reported in Nature Medicine (also part of the Nature group of journals) on their discovery relating to two other KwaZulu-Natal women, that a shift in the position of one sugar molecule on the surface of the virus led to the development of broadly neutralizing antibodies against HIV.

All HIV infected people respond to HIV by making antibodies. In most patients, these antibodies are not able to kill a wide range of HIV -- this is described as a lack of neutralization breadth. However, in a few infected people, they naturally make antibodies that kill (neutralize) many different kinds of HIV (i.e. they are broadly neutralizing antibodies).

"Broadly neutralizing antibodies have some unusual features," says Dr. Penny Moore, from Wits University and one of the lead South African scientists on the study based at the NICD. "The outer covering (envelope) of HIV has a coating of sugars that prevents antibodies from reaching the surface to neutralize the virus. In this patient, we found that her antibodies had 'long arms', which enabled them to reach through the sugar coat that protects HIV." In this study, the researchers found that these antibodies had 'long arms' right at the outset. "We discovered that some HIV antibodies are born with 'long arms', requiring less time and fewer changes to become effective in killing HIV," says Moore.

The identification and successful cloning of these special antibodies enables the researchers to make sufficiently large quantities for further testing, similar to the way a medicine used to prevent or treat HIV would be tested. "Our goal is to test these antibodies, preferably in combination with other broadly neutralizing antibodies, directly in patients with HIV infection or in patients at risk of getting infected," said Karim. "But this will take some time as the team is currently planning animal studies as a first step.

Broadly neutralizing antibodies have previously been shown to be effective in preventing and treating HIV infection in animals, but this has never before been shown in humans." The future studies on animals and humans are being supported by the Strategic Health Innovation Partnerships, a unit of the South African Medical Research Council, with funding from the Department of Science and Technology.

The Minister of Science and Technology, Mr. Derek Hanekom, commented: "This study highlights the importance of international scientific partnerships and the contributions of South African researchers to world-class medical science. The Department of Science and Technology is delighted to have contributed funds for this research. We are proud of the South African research team who conducted this ground-breaking study and thank the US partners for their collaboration and support."

The Minister of Health, Dr. Aaron Motsoaledi, pointed out: "Since South Africa has the largest burden of HIV infection globally, we are gratified to see South African scientists, under Professor Abdool Karim's leadership, undertake this research to find solutions that will bring an end to AIDS. We are hopeful that this research takes us one step closer to developing an AIDS vaccine."



NA Doria-Rose, CA Schramm, J Gorman, JR Mascola, et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature. March 2, 2014 (Epub).

Other Sources

Wits University. New Research on Potent HIV Antibodies. Press release. March 3, 2014.

National Institutes of Health. Study of antibody evolution charts course toward HIV vaccine. Press release. March 2, 2014.

CROI 2014: HIV Cure May Need Multiple Components, Workshop Delegates Hear

Delegates at the community cure workshop in advance of the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) this week in Boston might have been in a less hopeful frame of mind than they had been 7 months previously when, at the International AIDS Society conference in Kuala Lumpur, it looked as if 2 more people had joined "Berlin patient" Timothy Ray Brown in being cured of HIV, using a similar bone-marrow transplant technology.


CROI 2014: Retrovirus Conference Now Underway in Boston

The 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) kicked off in Boston this week with a program for young investigators, a press conference on new hepatitis C treatments, and opening lectures on HIV immune response and cross-species transmission and an update on the epidemic in West Africa. will be on site all week bringing you the latest news.alt

CROI 2014: Treatment as Prevention Dramatically Lowers HIV Sexual Transmission [VIDEO]

A large study of heterosexual and gay couples saw no cases of linked HIV transmission during 44,500 condomless sex acts when the positive partner was on combination antiretroviral therapy (ART) with suppressed viral load, according to a presentation at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) this week in Boston. Based on these findings, there is no reason for legal action against people not using condoms while on effective ART.


[Jens Lundgrenspeaks at CROI 2014 press conference, Boston, March 4, 2014]

Jens Lundgren from the University of Copenhagen reported the first findings from the PARTNER study, looking at HIV transmission within more than 750 serodiscordant couples -- together contributing nearly 900 years of follow-up -- who reported not using condoms.

While this much condomless vaginal and anal sex would be expected to lead to 50 to 100 transmissions, based on historical data, the researchers did not see any cases of linked transmission in which newly acquired HIV matched a partner's strain.

While the risk of transmission per sex act while on ART fell to nearly zero, the cumulative risk over time must still be considered. Lundgren said. Estimates of risk over 10 years may reach as high as 1 in 25 overall, or up to 1 in 10 for anal sex. Whether this level of risk is acceptable "is not for us to say, but for people to decide," he said.

Lundgren emphasized, however, that there is "no reasonable legal action you can take against people for not using condoms" if they are on effective ART, and no indication for post-exposure prophylaxis (PEP) in this situation.

These findings support the recent decision by the Centers for Disease Control and Prevention (CDC) -- at the urging of activists -- to refer to "condomless sex" rather than "unprotected sex," recognizing that there are other effective prevention approaches besides condom use.

See also:



A Rodger, T Bruun, V Cambiano, J Lundgren, et al. HIV Transmission Risk Through Condomless Sex If HIV+ Partner On Suppressive ART: PARTNER Study. Conference on Retroviruses and Opportunistic Infections (CROI 2014). Boston, March 3-6. Abstract 153LB.

Press conference. 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014). Boston. March 4, 2014.


CROI 2014: The Role of Interferon in HIV Response [VIDEO]

Although interferon is on its way out as a standard of care for hepatitis C, researchers are learning more about its role in HIV, conference vice chair Julie Overbaugh said at a media briefing on the opening day of the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) this week in Boston.


CROI 2014: No One with Undetectable Viral Load Transmits HIV in PARTNER Study

The second large study to look at whether people with HIV become non-infectious if they are on antiretroviral therapy (ART) has found no cases where someone with a viral load under 200 copies/mL transmitted HIV, either by anal or vaginal sex, researchers reported at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) this week in Boston.


CROI 2014: HIV in People Who Use Drugs [VIDEO]

Despite ample evidence that syringe exchange and opiate substitution therapy work to help prevent transmission of HIV and viral hepatitis, access remains "woefully inadequate" in most parts of the world, Adeeba Kamarulzaman from the University of Malaya said during her plenary talk at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) this week in Boston.