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A research article published in the journal Science has reported the efficacy of three different vaccine platforms against the Zika virus in rhesus macaque monkeys.
All our previous output on this subject can be seen here. The SMC also produced a Factsheet on the Zika virus.
Prof. Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:
“We knew that these vaccines worked in mice and now the researchers have shown that they also protect non-human primates from Zika virus infection.
“The next step will be to see if these vaccines are safe and the scientists hope to start early trials in humans to address this. But this isn’t so straightforward. A key issue is whether or not antibodies raised against the Zika vaccine can recognise other related viruses like dengue. If antibodies raised against the Zika vaccine also recognise these other related viruses then this can be a really big problem as we know that some cross reactive antibodies might actually enhance the infection of these viruses – certainly not something you want a vaccine to do!
“Another problem related to antibody cross-reactivity is that the vaccine might not work in individuals previously exposed to these related viruses as their existing antibodies may kill the vaccine before it has had a chance to work.
“So, whilst these vaccine studies are promising there are some really important questions that need to be addressed.”
Prof. Ian Jones, Professor of Virology, University of Reading, said:
“The demonstration of protection against Zika infection in rhesus monkeys is not unexpected but is nonetheless welcome as a further step on the road to a human vaccine.
“Of the three vaccines tested here, the simplest, inactivated virus is the most likely contender for a full human trial. Only when that is done will we know if one shot is sufficient, if previous or co-circulating infections have any adverse effect on the outcome, and how long protection might last.
“However, as a waymarker to a proven human vaccine this is about as good a result as you could wish for.”
Prof. Sarah Gilbert, Professor of Vaccinology, University of Oxford, said:
“This paper describes an important step in the development of a Zika virus vaccine. The authors have made three different vaccines by applying approaches that are often used in vaccine development; an inactivated Zika virus, a DNA vaccine and an adenoviral vectored vaccine. The first approach requires large quantities of Zika virus to be produced in order to make a vaccine whereas the second two use genes from the Zika virus within either the DNA or adenoviral vectored vaccine rather than using the whole virus.
“Not surprisingly the authors noticed different levels of immunogenicity in monkeys and in mice, with the DNA vaccine performing less well at inducing immune responses in monkeys. However all three vaccines protected the monkeys when they were deliberately exposed to the Zika virus.
“As the authors point out, despite the encouraging results there is a need for caution in proceeding with testing the vaccines in humans. It is known that antibodies against one serotype of the closely related dengue virus can make subsequent infections with a different serotype much more severe. It will be necessary to make sure that people receiving a Zika vaccine do not then become more susceptible to severe dengue infections, which can be fatal. The first clinical trials to be carried out will therefore require detailed studies to assess this risk using laboratory models of dengue infection to test the serum from people who receive the Zika vaccine.”
Dr Derek Gatherer, Lecturer in the Division of Biomedical and Life Sciences, Lancaster University, said:
“Abbink and co-authors report another step forward towards a commercial Zika vaccine, repeating earlier studies on mice in macaque monkeys, using an inactivated whole-virus vaccine and two lab-modified vaccines that only contain part of the Zika virus particle. The partial vaccines are potentially preferable to the whole-virus version for safety reasons and a similar approach has been used in the design of the successfully trialled Ebola vaccine in west Africa.
“None of the vaccine variants appears to have any adverse side effects and all are effective at protecting the monkeys from subsequent infection with Zika virus. Antibodies purified from vaccinated monkeys are also protective when injected into unvaccinated monkeys.
“Both Brazilian and Puerto Rican strains of Zika virus are used in the tests, but since these are both American variants of Zika, this leaves some important questions unanswered.
“Firstly, does vaccination with an African strain protect against infection with an Asian or American strain?
“Secondly, does previous infection with a geographically different Zika strain affect the reaction to the vaccine?
“Thirdly, does previous or subsequent infection with other flaviviruses such as dengue affect the reaction to the vaccine?
“Answers to these questions are crucial in order to predict the effect Asian/American Zika might have if it spreads to Africa, and also if Zika vaccination will, in some subjects, produce an adverse reaction similar to dengue shock syndrome. These questions are all answerable using the macaque model system the authors have set up, and we ought to be finding out the answers soon. If these answers are favourable, then human trials will not be far off.”
Dr Ed Wright, Senior Lecturer and Virologist, University of Westminster, said:
“Two of the vaccines used here have previously shown promise as they were able to protect mice from infection with Zika virus. The aim of the study reported today was to determine the effectiveness of three different Zika virus vaccines. One vaccine comprises Zika virus particles that have been inactivated, rendering them harmless. Another vaccine is a gene-based vaccine, containing the genetic information that encodes for the coat protein of the virus. The final vaccine is an innocuous monkey virus that, as with the gene-based vaccine, has been engineered to express the Zika virus coat protein.
“The authors administered each vaccine separately to monkeys and were able to detect a Zika virus specific immune response in all animals. The monkeys were subsequently infected with isolates of Zika viruses recovered from Brazilian and Puerto Rican individuals.
“All three vaccines were 100% protective, with no virus detected in any of the bodily fluids tested. This compares to the control group, who were not vaccinated, where virus was detected in all samples from all animals. No clinical safety issues were reported for any of the vaccines. Therefore, the next step will be human clinical trials that are likely to start in the coming weeks.
“Given the size of the outbreak in the Americas and the strong evidence of a causal link between Zika virus infection of pregnant women and neurological disorders in their unborn babies, the results of this study are welcome news. The development of an effective vaccine against Zika virus represents the best way to protect people at risk of complications following infection. However, all of the vaccines currently under development are many years away from being licensed and available for widespread public use.”
Prof. Ravindra Gupta, Wellcome Trust Senior Research Fellow in the UCL Department of Infection, UCL, and Honorary Consultant Infectious Diseases, UCLH, said:
“This study on protective efficacy of three Zika virus vaccines shows full protection for all three in a Rhesus Monkey model, representing an important advance that paves the way for trials in humans. The authors show that the vaccines generate potent antibodies against Zika that are the likely mechanism for protection.”
Dr Peter Barlow, British Society for Immunology spokesperson and Reader in Immunology & Infection at Edinburgh Napier University, said:
“There are a number of significant health concerns around Zika virus infection, most notably for pregnant women, and thus an effective and safe vaccine against this virus is urgently required.
“This study used three different vaccine approaches in rhesus monkeys in order to assess the effectiveness of the vaccines in terms of protecting them against Zika virus infection. The data showed that all three vaccine approaches offered complete protection against Zika virus infection in the rhesus monkeys, without any major side effects.
“This study represents a promising step forward in the rapid development of a safe and robust vaccine against Zika virus infection in humans. I would now expect clinical trials of a Zika vaccine in humans, using one or more of these approaches, to begin this year.”
‘Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys’ by Peter Abbink et al. published in Science on Thursday 4 August 2016.
Declared interests
Prof. Jonathan Ball, Prof. Ian Jones, Dr Derek Gatherer, Dr Ed Wright and Prof. Ravindra Gupta declared that they had no conflicts of interests.
Prof. Sarah Gilbert: “I work in vaccine development at the Jenner Institute, University of Oxford, which is also developing a Zika vaccine, and am scientific co-founder of Vaccitech, a spin-out company which uses adenoviral vectored vaccines but is not developing a Zika virus vaccine.”
Dr Peter Barlow: “Dr Peter Barlow is funded by the Chief Scientist Office of the Scottish Government leading a project examining novel antiviral therapeutics for Rhinovirus, but this does not relate to vaccine development or Zika. Around 5 years ago Peter worked for the US Centers for Disease Control and Prevention and was involved in experimental work of vaccines designed for influenza, but this was not commercial in nature.”