TWiV 408: Boston Quammens

Four years after filming ‘Threading the NEIDL’, Vincent and Alan return to the National Emerging Infectious Diseases Laboratory BSL4 facility at Boston University where they speak with science writer David Quammen.

You can find TWiV #408 at microbe.tv/twiv, or watch/listen here.

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TWiV 406: Pow, right in the enteroids!

The TWiV team discusses eye infections caused by Zika virus, failure of Culex mosquitoes to transmit the virus, and replication of norovirus in stem cell derived enteroids.

You can find TWiV #406 at microbe.tv/twiv, or listen below.

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TWiV 405: All the world’s a phage

The TWiXers discuss a study on vertical transmission of Zika virus by Aedes mosquitoes, and uncovering Earth’s virome by mining existing metagenomic sequence data.

You can find TWiV #405 at microbe.tv/twiv, or listen below.

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TWiV 402: The plight of the bumblebee

Polio returns to Nigeria, Zika virus spreads in Miami, and virus infection of plants attracts bumblebees for pollination, from the virus gentlepeople at TWiV.

You can find TWiV #400 at microbe.tv/twiv, or listen below.

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Zika Virus in the USA

On this episode of Virus Watch we cover three Zika virus stories: the first human trial of a Zika virus vaccine, the first local transmission of infection in the United States, and whether the virus is a threat to participants in the 2016 Summer Olympic and Paralympic Games.

TWiV 401: Vector victorious

Zika virus spreads in the USA, a Zika virus DNA vaccine goes into phase I trials, and how mosquito bites enhance virus replication and disease, from the friendly TWiFolk Vincent, Dickson, Alan, and Kathy.

You can find TWiV #401 at microbe.tv/twiv, or listen below.

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Antibodies aid dengue and Zika virus infection

Antibody dependent enhancementFlaviviruses are unusual because antibodies that cross-react with different viruses can enhance infection and disease. This property, called antibody-dependent enhancement or ADE, has been documented to occur among the four serotypes of dengue virus. It has implications for infection with or vaccination against Zika virus or dengue virus.

Earlier this year (virology blog link) it was shown that antibodies to dengue virus – in the form of serum from infected patients, or two human monoclonal antibodies – bind to Zika virus and can enhance infection of Fc-receptor bearing cells (Fc receptors bind the antibody molecule, allowing uptake into cells – illustrated). When the antibodies to dengue virus were omitted, Zika virus barely infected these cells. The conclusion is that dengue antibodies enhance infection of cells in culture by Zika virus.

This early work was first published as a preprint on the bioRxiv server – which lead some to criticize me for discussing the work before peer review. However, I subjected the paper to my own peer review, of which I am entirely capable, and decided it was worthy of discussion on this blog.

The results have now been confirmed by an independent group (paper link). Sera from patients that were infected with dengue virus, as well as dengue virus specific human monoclonal antibodies, were shown to bind Zika virus and enhance infection of Fc receptor bearing cells. These are the same findings of the group who first published on bioRxiv. That paper still has not been published – apparently it is mired in peer review, with many new experiments requested. I do hope that none of the authors of the second paper are involved in delaying its publication – something that happens all too often in science. As a colleague once remarked, ‘the main function of peer review is to prevent your competitors from publishing their work’.

Whether or not antibodies to dengue virus enhance Zika virus disease in humans is an important unanswered question.

If you are wondering whether antibodies to Zika virus can enhance dengue virus infection, the answer is yes (paper link). Monoclonal antibodies were isolated from four Zika virus-infected patients, and shown to enhance infection of Fc receptor bearing cells with either Zika virus or dengue virus. Furthermore, administration of these antibodies to mice before infection with dengue virus led to severe disease and lethality, a demonstration of antibody-dependent enhancement in an animal model.

Of interest is the finding that ADE mediated lethality in this mouse model can be completely prevented by co-administering the same antibody that has been modified to block binding to Fc receptors on cells. This result suggests a modality for treating patients with enhanced disease caused by either dengue virus or Zika virus.

These observations suggest that we need to be careful when deploying vaccines against Zika virus or dengue virus – it is possible that the antibody response could enhance disease. Recently a dengue virus vaccine called Dengvaxxia was approved for use in Brazil, Mexico, and the Philippines. However, the vaccine is not licensed for use in children less than 9 years of age because in clinical trials, immunization lead to more severe disease after infection compared with non-immunized controls. Analysis of the clinical trial data (paper link) indicates that seronegative individuals of all ages were at increased risk for developing severe disease that requires hospitalization. The authors suggest that severe disease is a consequence of enhancement of infection caused by antibodies induced by the vaccine (see CIDRAP article for more information).

These observations lead to the question of whether immunization against dengue and Zika viruses might enhance disease caused by either virus. Could a solution to this potential problem be to use a vaccine that combines the four serotypes of dengue virus with Zika virus? If so, the dengue virus component should not be Dengvaxia, but possibly another vaccine (e.g. TV003 – virology blog link) that does not induce disease enhancing antibodies.

Zika virus vaccine

The first experimental Zika virus vaccine has been published, and in this episode of Virus Watch, I explain how it works – it’s a DNA vaccine – and I compare it with all the other vaccines out there.

TWiV 399: Zika la femme

The latest Zika virus news from the ConTWiVstadors, including a case of female to male transmission, risk of infection at the 2016 summer Olympics, a DNA vaccine, antibody-dependent enhancement by dengue antibodies, and sites of replication in the placenta.

You can find TWiV #399 at microbe.tv/twiv, or listen below.

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Congress fails on Zika virus

Zika virusAndrew W. Gurman, M.D., President of the American Medical Association, has expressed disappointment in the failure of Congress to support the US public health response to Zika Virus:

At a time when concerns continue to mount about the nation’s readiness to protect the public from the Zika virus, the AMA is disappointed by Congress’ failure to pass legislation before adjourning for summer recess that would provide the resources necessary for our country to respond to this looming public health crisis.

Without ensuring there are sufficient resources available for research, prevention, control and treatment of illnesses associated with the Zika virus, the United States will be ill-equipped to deploy the kind of public health response needed to keep our citizens safe and healthy—especially since the spread of mosquito-borne illness is accelerated during the summer months.

I could not agree more with the AMA – Congress has so far failed to do the right thing with respect to Zika virus. Even if the virus does not spread within the continental United States, this country has an obligation to be a leader in scientific research that would benefit the entire world. Zika virus is clearly a threat to other parts of the globe, and by refusing to fund research on this virus, Congress is sending the message that it doesn’t care about the health problems of others.