The Next Vaccine For Pregnant Women

In case you hadn’t heard, there’s a new vaccine that will likely be marketed toward pregnant women within the next couple of years. It’s for Respiratory Syncytial Virus (RSV) in the newborn – a common cold-like illness that is usually mild in healthy people. Nearly all children will have had an infection by their second birthday – according to the CDC. Of those who have an infection before 6mths of age, approximately 1-2% will be hospitalised, due to complications such as bronchiolitis or pneumonia [1].

The quest for an RSV vaccine actually began decades ago…and it had disastrous beginnings.

In the early 1960’s, an RSV vaccine, propagated on human embryonic kidney cells, then passaged through monkey cells, before being inactivated with formalin, and adjuvanted with aluminium, was trialled on infants, with disastrous results. Up to 80% of vaccinated infants were hospitalized with severe lower-respiratory infections, and two babies died [2].

It took nearly four decades to figure out why the vaccine had such tragic results – which just goes to show how little is understood about the very system they seek to tamper with. It was due to “Lack of antibody affinity maturation followed poor Toll-like receptor stimulation”, according to the paper, published in Nature journal, in 2009 [3].

The quest for an RSV vaccine resumed with gusto.

At the forefront of the charge for an RSV vaccine, is Novavax, a biotechnology company with several products currently in the clinical testing stages. Following the announcement of positive results of Phase 2 clinical trials in older adults, in 2015, CEO of Novavax, Stanley Erck declared their RSV vaccine could be “the largest selling vaccine in the history of vaccines in terms of revenue” [4].

Unfortunately, the Phase 3 trial in older adults failed to show efficacy, and the company lost more than $1.5 billion in market value within hours of the announcement, as disappointed investors pulled their money [5].

This gives us some idea of the immense pressure faced by companies to come up with the next new ‘blockbuster’ vaccine. For a company like Novavax, with no products on the market yet, (just the potential of new products), investor confidence is necessary to finance the lengthy clinical trial and regulatory approval process.

Novavax then turned their attention to pregnant women, and in February 2019, announced favourable results (actually, not as favourable as they were hoping for, but nevertheless, they found a way to put a positive spin on them) from a Phase 3 clinical trial on pregnant women. The vaccine, called ‘Resvax’, is not only aluminium adjuvanted, it is also genetically-engineered with nano-particles. The press release stated “Our next steps include meeting with U.S. and European regulators to review these data and to discuss the path forward for licensure” [6].

The trials on pregnant women were funded, in part, by an $89 million grant from the Bill and Melinda Gates Foundation, with the stated purpose “to advance to WHO Pre-Qualification the development of a respiratory syncytial virus (RSV) vaccine for maternal immunization to reduce the burden of RSV disease in infants less than six months of age in developing countries” [7-8].

Obviously, the burden of RSV disease falls mainly on developing nations, however, it’s likely that a new RSV vaccine will also be targeted at pregnant women in western countries.

One of the important ways to prevent respiratory disease in infants is via breastfeeding. A study published in British Medical Journal found that among 115 babies who had been hospitalized for RSV infection, only 8 were breastfed [9].

Given that breastfeeding rates are vastly lower in developing countries, I can’t help but wonder why $89 million (and more) wasn’t spent to increase maternal nutrition and breastfeeding rates? For example, in West/Central Africa, only a mere 20% of infants are exclusively breastfed for the first six months of their life [10].

One of the main groups promoting the need for an RSV vaccine during pregnancy, is the Oxford Vaccine Group, who note that almost all infant deaths due to RSV are in developing countries [11].

The director of Oxford Vaccine Group is Andrew Pollard, who holds several vaccine-related patents [12-13], and is Chair of the UK Department of Health’s Joint Committee on Vaccination and Immunisation, and the European Medicine Agency’s scientific advisory group.

Another member of the group, Matthew Snape, has been Principal Investigator in clinical trials of numerous RSV vaccine candidates. He is also the Director of the National Immunization Schedule Evaluation Consortium (NISEC) [14].

It is also interesting to note that the CDC has held a patent for an RSV vaccine, since 2010 [15]. How might that affect any future decisions regarding RSV vaccinations being promoted to pregnant women?

References:

[1] CDC, Respiratory Syncytial Virus Infection (RSV), https://www.cdc.gov/rsv/high- risk/infants-young-children.html. Accessed March 2019.

[2] Dudas RA, Karron RA. Respiratory syncytial virus vaccines. Clin Microbiol Rev. 1998;11(3):430-9.

[3] Delgado MF, Coviello S, Monsalvo AC, et al. Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat Med. 2008;15(1):34-41.

[4] FierceBiotech, Novavax craters after phase III RSV F vaccine failure; seeks path forward, https://www.fiercebiotech.com/biotech/novavax-craters-after-phase-iii-rsv-f-vaccine-failure- seeks- path-forward. Accessed March 2019.

[5] CNBC, Novavax is down 80%. Here’s why its been really hard to develop an RSV vaccine, https://www.cnbc.com/2016/09/16/heres-why-its-been-really-hard-to-develop-a-vaccine-for- rsv.html. Accessed March, 2019.

[6] Novavax, Press Release: Novavax announces topline results from Phase 3 PrepareTM Trial of Resvax TM for prevention of RSV disease in infants via maternal immunization, http://ir.novavax.com/news-releases/news-release- details/novavax-announces-topline-results-phase-3-preparetm-trial. Accessed March 2019.

[7] Novavax, Bill & Melinda Gates Foundation, https://novavax.com/page/19/bill-and- melinda-gates-foundation. Accessed March 2019.

[8] Bill and Melinda Gates Foundation,How We Work, Grant: Novavax, Inc, https://www.gatesfoundation.org/How-We-Work/Quick-Links/Grants- Database/Grants/2015/09/OPP1127647. Accessed March 2019.

[9] Downham MA, Scott R, Sims DG, Webb JK, Gardner PS. Breast- feeding protects against respiratory syncytial virus infections. Br Med J. 1976;2(6030):274-6.

[10] UNICEF Progress for Children, Nutrition Indicators: Exclusive Breastfeeding, https://www.unicef.org/progressforchildren/2006n4/index_breastfeeding.html. Accessed March 2019.

[11] Oxford Vaccine Group: Vaccine Knowledge Project, Respiratory Syncytial Virus, http://vk.ovg.ox.ac.uk/rsv. Accessed April 2019.

[12] Justia Patents, Vaccine, https://patents.justia.com/patent/20130089571, Accessed April 2019.

[13] Justia Patents, Compositions comprising OPA Protein Epitopes, https://patents.justia.com/patent/20100183676. Accessed April 2019.

[14] Oxford Vaccine Group, Matthew Snape, https://www.ovg.ox.ac.uk/team/matthew-snape. Accessed April 2019.

[15] Anti-RSV Immunogens and methods of Immunization, https://patents.google.com/patent/US8846056?oq=vaccine+inassignee:centers+inassignee:f or+inas signee:disease+inassignee:control. Accessed April 2019.

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