The Covid-19 Prevention Network (CovPN) is in the process of establishing Covid-19 vaccine correlates of protection, with the first wave of information likely to be reported as soon as in six to eight weeks, a source familiar with the study said. The first wave of information will pertain to Moderna’s mRNA-1273 vaccine, with Johnson & Johnson’s (J&J’s) single-dose JNJ-78436735 to follow, he added.
Correlative data linking immunogenicity results and likelihood of protection is one of the most sought-after pieces of information in Covid-19 vaccine development. In the CovPN study, laboratory assays are currently being performed in hundreds of blood draws from Phase III trial participants, with biostatisticians finalising statistical models to study assay data, the source said. Once assay information is available, the data will be plugged into these models, with results to be analysed thereafter, he added.
Correlates of protection could do away with large-scale Phase III Covid-19 vaccine trials, specifically if there are necessary alterations to already authorised vaccines. Correlates of protection would also open authorisation in additional population subgroups not recruited in the Phase III trials.
CovPN, which was established in July 2020, was formed by the National Institutes of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) to conduct Phase III efficacy trials investigating Covid-19 vaccines and monoclonal antibodies. Vaccines that have not yet been authorised by the FDA, such as the University of Oxford/AstraZeneca’s AZD1222 and Novavax’s NVX-CoV2373, are a part of the network, according to the CovPN website. The only other Covid-19 vaccine with an FDA emergency use authorisation (EUA), Pfizer/BioNTech’s Comirnaty (BNT162b2), is not listed.
CovPN did not respond to a comment request.
Blood samples from vaccinated, infected trial participants highly informative
Assays are being performed in blood draws from vaccinated yet infected Phase III participants, the source said. There are four to five times more samples being studied from vaccinated, noninfected participants, he added. In the mRNA-1273 and JNJ-78436735 trials, infection events are counted 14 days after completion of the vaccination schedule.
Finding correlates of protection may be challenging due to the limitations of the available results, specifically since there are only a handful of vaccinated, infected participants, this news service reported on 21 January. Double-dose mRNA-1273 has 94.1% efficacy at preventing Covid-19 illness, based on 11 events in the mRNA-1273 cohort and 185 infection events in the placebo group (Baden, L., et al., N Engl J Med. 2021 Feb 4, 384(5), 403-416). Single-dose JNJ-78436735 is 66.9% effective at preventing moderate-to-severe Covid-19, based on 116 infection events in the vaccine arm and 348 events in the placebo arm, according to a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting document.
Data from infected, vaccinated people is highly informative as their infections are caused by lower immune response to the vaccine, the source said. Additionally, focusing the analysis on vaccinated participants is a judicious one, with Phase III trials having blood samples from thousands of volunteers, he added. Moderna’s Phase III trial enrolled 30,420 volunteers, while J&J’s Phase III ENSEMBLE trial recruited 43,783 people. US-based Phase III trials studying Oxford/AstraZeneca’s AZD1222 and Novavax’s NVX-CoV2373 have completed recruitment of 32,4000 and 30,000 participants, respectively.
The two-dose vaccine mRNA-1273 requires three blood draws per individual, the source noted. The first is collected before the first jab, the second is collected right before the second jab, and the third is collected two to four weeks after vaccination schedule completion, he added. There would only be two blood draws from the single-dose JNJ-78436735 vaccine, he said. The mRNA-1273 doses are administered 28 days apart. A two-dose schedule of JNJ-78436735 with a 57-day dosing gap is also under investigation in the Phase III ENSEMBLE 2 trial, which is still enrolling, according to ClinicalTrials.gov.
According to a 116-page statistical analysis plan for the study, laboratory assays measure binding antibodies to the SARS-CoV-2 spike protein, pseudovirus neutralising antibodies, and wild-type live virus neutralising antibodies. There are no cellular immunity markers under analysis because there are no peripheral blood mononuclear cell samples, the source added. Samples from the vaccinated, noninfected group are randomly selected, but there are systems in place to ensure samples from a wide variety of volunteers are analysed, he noted.
Nebulous if universal correlates of protection identifiable
It is currently unclear if there is one correlate of protection data for each individual vaccine, one that would apply to all vaccines, or one benchmark for each vaccine technology, the source noted. mRNA-1273 is an mRNA vaccine, while JNJ-78436735 and AZD1222 feature an adenovirus vector and NVX-CoV2373 is a protein subunit vaccine. J&J has its eyes on the New England Journal of Medicine to publish its Phase III ENSEMBLE trial manuscript for a likely release this month, this news service reported on 8 March.
Establishing correlates for protection could hold the key to many questions in Covid-19 vaccine development. For example, correlates for protection data for mRNA-1273 would allow the potential for straightforward authorisation of a 50μg dose of the vaccine, as it is currently authorised at a 100μg dose, this news service reported 21 January. Additionally, a new version of an authorised vaccine may only need noninferior immunogenicity data versus its older version to address variants of concern, with this approach bolstered if there are correlates of protection data, this news service reported on 11 February.
Correlates for protection would also make authorisations straightforward in more population subgroups. Immunogenicity and safety Covid-19 vaccine results in adults are likely to correlate with vaccine receivers ages 12–16 years old, with correlates of protection data strengthening this authorisation pathway, this news service reported on 9 December.
Reynald Castaneda is an Associate Editor for Clinical Trials Arena parent company GlobalData’s investigative journalism team. A version of this article originally appeared on the Insights module of GlobalData’s Pharmaceutical Intelligence Center. To access more articles like this, visit GlobalData.