While specific COVID-19 vaccines are helping to lower hospitalization rates and save lives during the novel coronavirus pandemic, unrelated vaccines also can help, according to a new study.

An article published in the Proceedings of the National Academy of Sciences suggests that the generalized immune-boosting properties of many vaccines can cross-protect patients against multiple pathogens.

Weill Cornell Medicine and the University of Oxford–led researchers recount how before highly effective COVID-19 vaccines became available, some public health experts and immunologists suggested immunizing vulnerable populations with other vaccines to provide some degree of protection.

'We know that unrelated vaccines have these heterologous effects, and a reasonable person could tell you that if you used them during a pandemic, it would benefit," states lead author Nathaniel Hupert, MD, MPH, associate professor of population health sciences at Weill Cornell Medicine. "However, it wasn't clear how much such an intervention would help, which populations would be best to target or how much of the population would have to get the unrelated vaccines to have a meaningful effect."

The study points out that the COVID-19 pandemic has been difficult to control because of the lagging global uptake of targeted vaccines, the emergence of more transmissible variants, and resistance to compliance with nonpharmaceutical interventions.

"Commonly used vaccines can have nonspecific immune effects, and several have been shown to have beneficial heterologous effects against SARS-CoV-2 infection," the researchers added. "However, there is no science-based guidance on effective implementation of such heterologous vaccine interventions (HVIs) to counter the current or future pandemics."

To remedy that, the study team created a model looking at a range of HVI strategies on the winter 2020 COVID-19 wave in the U.S. The results suggest that targeting both elderly and nonelderly populations and intervening during pandemic growth phases—essentially when the effective reproduction number is greater than 1—created the greatest reduction in morbidity and mortality.

"Decades of theoretical and experimental data suggest that nonspecific effects of nonÐCOVID-19 vaccines may help bolster population immunological resilience to new pathogens" the authors explained. "These routine vaccinations can stimulate heterologous cross-protective effects, which modulate nontargeted infections. For example, immunization with Bacillus-Calmette-Guérin, inactivated influenza vaccine, oral polio vaccine, and other vaccines have been associated with some protection from SARS-CoV-2 infection and amelioration of COVID-19 disease. If heterologous vaccine interventions are to be seriously considered by policymakers as bridging or boosting interventions in pandemic settings to augment nonpharmaceutical interventions and specific vaccination efforts, evidence is needed to determine their optimal implementation."

The study employed the COVID-19 International Modeling Consortium mathematical model to show "that logistically realistic HVIs with low (5% to 15%) effectiveness could have reduced COVID-19 cases, hospitalization, and mortality in the United States fall/winter 2020 wave."

Researchers caution, however, that similar to other mass drug administration campaigns, HVI impact is influenced by age targeting and intervention timing. They conclude that maximal benefit occurs when the program is implemented among the widest age cohort before the pandemic is completely out of control.

"Optimal HVI logistics, therefore, differ from optimal rollout parameters for specific COVID-19 immunizations," researchers explained, "These results may be generalizable beyond COVID-19 and the US to indicate how even minimally effective heterologous immunization campaigns could reduce the burden of future viral pandemics."

The researchers did not specify a particular vaccine but chose values for cross-protection consistent with data from earlier studies on measles, influenza, tuberculosis, and other immunizations. They determined that an unrelated vaccine that provided just 5% protection against serious COVID-19 and was delivered to a small portion of the population would still have helped reduce caseloads and hospital admissions substantially.

"Surprisingly, we found a couple of really interesting emergent results from what we put in the mix," Dr. Hupert stated. Even though COVID-19 severity correlates tightly with age, their experimental scenario that modeled vaccinating everyone older than age 20 years was more effective than strategies targeting only the elderly. This is possibly because younger people tend to have more social contacts and personal interactions.

Dr. Hupert points out that with emergency variants, it is necessary to research "each and every additional protective measure that we can muster across populations at risk—even small ones like those we modeled—will lead to fewer infections, which means fewer new variants, which may mean a quicker end to the pandemic."

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