How Well Do COVID Vaccines Mix and Match Together?

 A "mix and match" booster strategy with a variety of different COVID-19 vaccines was safe and boosted immune response following primary series vaccinations with either Pfizer or AstraZeneca's shots, U.K. researchers found.

In addition to Pfizer and AstraZeneca, the study found acceptable immune responses and safety profiles among five other vaccines when used as boosters after the two-dose Pfizer or AstraZeneca primary series (Moderna, Johnson & Johnson, Novavax, Valneva, CureVac), reported Saul Faust, MD, of NHS Foundation Trust in Southampton, England, and colleagues in The Lancet.

"The side effect data show all seven vaccines are safe to use as third doses, with acceptable levels of inflammatory side effects like injection site pain, muscle soreness, fatigue," said Faust in a statement. He noted that all seven vaccines boosted spike protein immunogenicity after the AstraZeneca primary series, and all vaccines but Valneva did so after the Pfizer primary series. Boosters in the study were given a few months after the primary series.

The FDA approved heterologous "mix and match" boosters in October. However, this decision was made on the basis of preprint data that was not peer-reviewed. CDC currently recommends that all adults receive a booster dose of COVID vaccine at least 6 months after a Pfizer or Moderna two-dose primary series or at least 2 months after a Johnson & Johnson primary shot.

Faust's group conducted the phase II COV-BOOST trial in adults ages 30 and up who were at least 70 days post-AstraZeneca vaccine or 84 days post-Pfizer vaccine and had no history of laboratory-confirmed COVID-19. They were split into three groups, and each group was randomized to either vaccine or control arms.

• Group A received Novavax, half-dose of Novavax, AstraZeneca, or placebo (MenACWY vaccine)
• Group B received Pfizer, Valneva, half-dose of Valneva, Johnson & Johnson, or placebo
• Group C received Moderna, CureVac, half-dose of Pfizer, or placebo

From June 1 to June 30, 2,878 participants met eligibility criteria. They were divided into groups by age: 30 to 69 and 70 and up. Median age in the younger age group was 51 to 53, and in the older age group, it was 76 to 78. Nearly all were white.

Not surprisingly, reactogenicity was greater in adults ages 30 to 69 compared with those ages 70 and up. Fatigue and headache were the most common systemic reactions. Interestingly, those in the Pfizer group who were boosted with Moderna, CureVac, AstraZeneca, or Johnson & Johnson reported more local and systemic reactions than other vaccines and control.

Of 912 participants, 1,306 adverse events were reported, including 20 adverse events of special interest occurring within 14 days after the third dose, six of which were "possibly" related to the vaccine. There were 24 serious adverse events, and 21 participants reported a positive PCR test for SARS-CoV-2, with no hospitalization.

Geometric mean titers increased in all participants at 28 days post-vaccination versus controls for anti-spike IgG, with increases ranging from 1.3 for a half-dose of Valneva to 11.5 for Moderna following a Pfizer primary series.

Examining T-cell response, Faust's group noted that the T-cell boosting effects of Novavax and half-dose of Novavax were lower in those who received a Pfizer versus an AstraZeneca primary series, adding, "The geometric mean of T-cell responses in the half [Novavax] group was not significantly higher than control."

They said there was a "good correlation" for all vaccines between the pseudoneutralizing assay against the wild-type and Delta variants at day 0 and 28.

"Vaccines that produce antibodies against wild-type appear to neutralize Delta effectively in vitro to a consistent, but slightly lesser degree, confirming the current public health strategy of using wild-type vaccines to control the currently predominant Delta epidemic," they wrote.

They also noted that half-doses of vaccines had "minimal decrease on immunogenicity by anti-spike IgG and neutralizing assays."

"If immunogenicity can be maintained in larger dose reduction studies, this could significantly increase the numbers of doses available globally," they added.

Limitations to the study included a shorter interval from second doses to boosters, given the need to generate policy data, as well as a lack of generalizability to younger populations. These results are applicable only in a 28-day timeframe, Faust and colleagues said.

"Further work will generate data at 3 months and 1 year after people have received their boosters, which will provide insights into their impact on long-term protection and immunological memory," Faust said. "We are also studying two of the vaccines in people who had a later third dose after 7-8 months, although results will not be available until the new year."

Disclosures

This study was supported by the UK Vaccine Taskforce and National Institute for Health Research.

Faust acts on behalf of University Hospital Southampton National Health Service Foundation Trust on vaccine clinical trials from Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck, and Valneva.

Other co-authors disclosed support from AstraZeneca, GlaxoSmithKline, Janssen, Medimmune, Merck, Pfizer, Sanofi, Valneva, Boehringer Ingelheim, Chiesi, Cipla, Teva, Medicago, and Novavax.

One co-author is named as inventor on a patent on an ingredient in the AstraZeneca vaccine.

Primary Source

The Lancet

Source Reference: Munro APS, et al "Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial" Lancet 2021; DOI: 10.1016/S0140-6736(21)02717-3.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/95988